Molecular Oncology
Volume 3, Issue 2 , Pages 97-137 , April 2009

Hereditary ovarian carcinoma: Heterogeneity, molecular genetics, pathology, and management

  • Henry T. Lynch

      Affiliations

    • Department of Preventive Medicine and Public Health, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 402 280 2942; fax: +1 402 280 1734.
  • ,
  • Murray Joseph Casey

      Affiliations

    • Department of Gynecology and Obstetrics, Creighton University Medical Center, Omaha, NE 68131, USA
  • ,
  • Carrie L. Snyder

      Affiliations

    • Department of Preventive Medicine and Public Health, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
  • ,
  • Chhanda Bewtra

      Affiliations

    • Department of Pathology, Creighton University Medical Center, Omaha, NE 68131, USA
  • ,
  • Jane F. Lynch

      Affiliations

    • Department of Preventive Medicine and Public Health, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
  • ,
  • Matthew Butts

      Affiliations

    • Department of Preventive Medicine and Public Health, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
  • ,
  • Andrew K. Godwin

      Affiliations

    • Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA

Received 2 February 2009 ,Revised 3 February 2009 ,Accepted 6 February 2009.

References 

  1. Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin J-P, et al. Clues to the pathogenesis of familial colorectal cancer. Science. 1993;260:812–816
  2. Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomäki P, et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N. Engl. J. Med. 1998;338:1481–1487
  3. Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int. J. Cancer. 1999;81:214–218
  4. Acharya S, Wilson T, Gradia S, Kane MF, Guerrette S, Marsischky GT, et al. hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc. Natl. Acad. Sci. U.S.A. 1996;93:13629–13634
  5. Agoff SN, Mendelin JE, Grieco VS, Garcia RL. Unexpected gynecologic neoplasm in patients with proven or suspected BRCA-1 or -2 mutations: implications for gross examination, cytology, and clinical follow-up. Am. J. Surg. Pathol. 2002;26:171–178
  6. Aida H, Takakuwa K, Nagata H, Tsuneki I, Takano M, Tsuji S, et al Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1. Clin. Cancer Res. 1998;4:235–240
  7. Akiyama Y, Sato H, Yamada T, Nagasaki H, Tsuchiya A, Abe R, et al. Germ-line mutation of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred. Cancer Res. 1997;57:3920–3923
  8. Ali-Fehmi R, Khalifeh I, Bandyopadhyay S, Lawrence WD, Silva E, Liao D, et al. Patterns of loss of heterozygosity at 10q23.3 and microsatellite instability in endometriosis, atypical endometriosis, and ovarian carcinoma arising in association with endometriosis. Int. J. Gynecol. Pathol. 2006;25:223–229
  9. Antoniou AC, Gayther SA, Stratton JF, Ponder BAJ, Easton DF. Risk models for familial ovarian and breast cancer. Genet. Epidemiol. 2000;18:173–190
  10. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 and BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am. J. Hum. Genet. 2003;72:1117–1130
  11. Arboleda MJ, Lyons JF, Kabbinavar FF, Bray MR, Snow BE, Ayala R, et al. Overexpression of AKT2/protein kinase Bβ leads to up-regulation of β1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells. Cancer Res. 2003;63:196–206
  12. Auersperg N, Wong AS, Choi KC, Kang SK, Leung PC. Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr. Rev. 2001;22:255–288
  13. Aziz S, Kuperstein G, Rosen B, Cole D, Nedelcu R, McLaughlin J, et al. A genetic epidemiological study of carcinoma of the fallopian tube. Gynecol. Oncol. 2001;80:341–345
  14. Baldwin RL, Nemeth E, Tran H, Shvartsman H, Cass I, Narod S, et al. BRCA1 promoter region hypermethylation in ovarian carcinoma: a population-based study. Cancer Res. 2000;60:5329–5333
  15. Bassis ML. An embryologically derived classification of ovarian tumors. JAMA. 1960;174:1316–1319
  16. Beiner ME, Finch A, Rosen B, Lubinski J, Moller P, Ghadirian P, et al. The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations. A prospective study. Gynecol. Oncol. 2007;104:7–10
  17. Bell DA. Origins and molecular pathology of ovarian cancer. Modern Pathol. 2005;18(Suppl. 2):S19–S32
  18. Bell R, Petticrew M, Sheldon T. The performance of screening tests for ovarian cancer: results of a systematic review. Br. J. Obstet. Gynaecol. 1998;105:1136–1147
  19. Bellacosa A, de Feo D, Godwin AK, Bell DW, Cheng JQ, Altomare DA, et al. Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int. J. Cancer. 1995;64:280–285
  20. Ben David Y, Chetrit A, Hirsh-Yechezkel G, Friedman E, Beck BD, Beller U, et al Effect of BRCA mutations on the length of survival in epithelial ovarian tumors. J. Clin. Oncol. 2002;20:463–466
  21. Bergman L, Beelen ML, Gallee MP, Hollema H, Benraadt J, van Leeuwen FE. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of liver and endometrial cancer risk following tamoxifen. Lancet. 2000;356:881–887
  22. Bernstein L, Deapen D, Cerhan J, Schwartz SM, Liff J, McGann-Maloney E, et al. Tamoxifen therapy for breast cancer and endometrial cancer risk. J. Natl. Cancer Inst. 1999;91:1654–1662
  23. Bewtra C, Watson P, Conway T, Read-Hippee C, Lynch HT. Hereditary ovarian cancer: a clinicopathological study. Int. J. Gynecol. Pathol. 1992;11:180–187
  24. Biron-Shental T, Drucker L, Altaras M, Bernheim J, Fishman A. High incidence of BRCA1-2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinoma. Eur. J. Surg. Oncol. 2006;32:1097–1100
  25. Boland CR, Koi M, Chang DK, Carethers JM. The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside. Fam. Cancer. 2008;7:41–52
  26. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–5257
  27. Borg A, Isola J, Chen J, Rubio C, Johansson U, Werelius B, et al. Germline BRCA1 and HMLH1 mutations in a family with male and female breast carcinoma. Int. J. Cancer. 2000;85:796–800
  28. Bosse K, Rhiem K, Wappenschmidt B, Hellmich M, Madeja M, Ortmann M, et al. Screening for ovarian cancer by transvaginal ultrasound and serum CA125 measurement in women with a familial predisposition: a prospective cohort study. Gynecol. Oncol. 2006;103:1077–1082
  29. Bourne TH, Campbell S, Reynolds KM, Whitehead MI, Hampson J, Royston P, et al. Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging. BMJ. 1993;306:1025–1029
  30. Boyd J. Molecular genetics of hereditary ovarian cancer. Oncology. 1998;12:399–406
  31. Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, et al Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA. 2000;283:2260–2265
  32. Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary nonpolyposis colon cancer. Nature. 1994;368:258–261
  33. Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J. Natl. Cancer Inst. 2002;94:1365–1372
  34. Brown GJ, St. John DJ, Macrae FA, Aittomaki K. Cancer risk in young women at risk of hereditary nonpolyposis colorectal cancer: implications for gynecologic surveillance. Gynecol. Oncol. 2001;80:346–349
  35. Buller RE, Shahin MS, Geisler JP, Zogg M, De Young BR, Davis CS. Failure of BRCA1 dysfunction to alter ovarian cancer survival. Clin. Cancer Res. 2002;8(5*):1196–1202(*Due to a page numbering error, an unrelated article with this same volume and start page citation appears in the 8(4) issue of Clin. Cancer Res.)
  36. Byrd LM, Shenton A, Maher ER, Woodward E, Belk R, Lim C, et al. Better life expectancy in women with BRCA2 compared with BRCA1 mutations is attributable to lower frequency and later onset of ovarian cancer. Cancer Epidemiol. Biomarkers Prev. 2008;17:1535–1542
  37. Cai KQ, Albarracin C, Rosen D, Zhong R, Zheng W, Luthra R, et al. Microsatellite instability and alteration of the expression of hMLH1 and hMSH2 in ovarian clear cell carcinoma. Hum. Pathol. 2004;35:552–559
  38. Cai KQ, Klein-Szanto A, Karthik D, Edelson M, Daly MB, Ozols RF, et al. Age-dependent morphological alterations of human ovaries from populations with and without BRCA mutations. Gynecol. Oncol. 2006;103:719–728
  39. Callahan MJ, Crum CP, Medeiros F, Kindelberger DW, Elvin JA, Garber JE, et al. Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J. Clin. Oncol. 2007;25:3985–3990
  40. Canistra SA. BRCA mutations and survival in women with ovarian cancer. N. Engl. J. Med. 1997;336:1254;(letter)
  41. Carethers JM, Hawn MT, Chauhan DP, Luce MC, Marra G, Koi M, et al. Competency in mismatch repair prohibits clonal expansion of cancer cells treated with N-methyl-N′-nitro-N-nitrosoguanidine. J. Clin. Invest. 1996;98:199–206
  42. Casarsa S, Puglisi F, Baudi F, De Paola L, Venuta S, Piga A, et al. BRCA2 germline mutations in primary cancer of the fallopian tube. Oncol. Rep. 2004;12:313–316
  43. Casey MJ. Estrogens, menopause and cancer. Conn. Med. 1977;41:776
  44. Casey MJ, Bewtra C. Peritoneal carcinoma in women with genetic susceptibility: implications for Jewish populations. Fam. Cancer. 2004;3:265–281
  45. Casey MJ, Bewtra C, Garcia-Padial J, Lynch HT. Laparoscopic examination and assisted bilateral salpingo-oophorectomy hysterectomy for prophylactic removal of the ovaries and uterus in women at genetic risk for ovarian cancer. J. Gynecol. Tech. 1995;1:111–114
  46. Casey MJ, Bewtra C, Hoehne LL, Tatpati AD, Lynch HT, Watson P. Histology of prophylactically removed ovaries from BRCA1 and BRCA2 mutation carriers compared with noncarriers in hereditary breast ovarian cancer syndrome kindreds. Gynecol. Oncol. 2000;78:278–287
  47. Casey MJ, Garcia-Padial J, Johnson C, Osborne NG, Sotolongo J, Watson P. A critical analysis of laparoscopic assisted vaginal hysterectomies compared with vaginal hysterectomies unassisted by laparoscopy and transabdominal hysterectomies. J. Gynecol. Surg. 1994;10:7–14
  48. Casey MJ, Madden TJ. Gravlee jet irrigator as a screening method?. JAMA. 1976;236:2051–2052
  49. Casey MJ, Snyder C, Bewtra C, Narod SA, Watson P, Lynch HT. Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations. Gynecol. Oncol. 2005;97:457–467
  50. Cass I, Baldwin RL, Varkey T, Moslehi R, Narod SA, Karlan BY. Improved survival in women with BRCA-associated ovarian carcinoma. Cancer. 2003;97:2187–2195
  51. Cass I, Holschneider C, Datta N, Barbuto D, Walts AE, Karlan BY. BRCA-mutation-associated fallopian tube carcinoma: a distinct clinical phenotype?. Obstet. Gynecol. 2005;106:1327–1334
  52. Catasús L, Bussaglia E, Rodríguez I, Gallardo A, Pons C, Irving JA, et al. Molecular genetic alterations in endometrioid carcinomas of the ovary: similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas. Hum. Pathol. 2004;35:1360–1368
  53. Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW, et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evalutation. Breast Cancer Res. Treat. 2001;65:125–134
  54. Chang DK, Ricciardiello L, Goel A, Chang CL, Boland CR. Steady-state regulation of the human DNA mismatch repair system. J. Biol. Chem. 2000;275:18424–18431
  55. Chang J, Powles TJ, Ashley SE, Gregory RK, Tidy VA, Teleaven JG, et al. The effect of tamoxifen and hormone replacement therapy on serum cholesterol, bone mineral density and coagulation factors in healthy postmenopausal women participating in a randomized, controlled tamoxifen prevention study. Ann. Oncol. 1996;7:671–675
  56. Chen X, Truong TT, Weaver J, Bove BA, Cattie K, Armstrong BA, et al. Intronic alterations in BRCA1 and BRCA2: effect on mRNA splicing fidelity and expression. Hum. Mutat. 2006;27:427–435
  57. Chen X, Weaver J, Bove BA, Vanderveer LA, Weil SC, Miron A, et al. Allelic imbalance in BRCA1 and BRCA2 gene expression is associated with an increased breast cancer risk. Hum. Mol. Genet. 2008;17:1336–1348
  58. Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, et al. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc. Natl. Acad. Sci. U.S.A. 1992;89:9267–9271
  59. Chetrit A, Hirsh-Yechezkel G, Ben-David Y, Lubin F, Friedman E, Sadetzki S. Effect of BRCA1/2 mutations on long-term survival of patients with invasive ovarian cancer: the national Israeli study of ovarian cancer. J. Clin. Oncol. 2008;26:20–25
  60. Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer. 1996;77:2318–2324
  61. Clendenning M, Baze ME, Sun S, Walsh K, Liyanarachchi S, Fix D, et al. Origins and prevalence of the American founder mutation of MSH2. Cancer Res. 2008;68:2145–2153
  62. Colgan TJ, Murphy J, Cole DE, Narod S, Rosen B. Occult carcinoma in prophylactic oophorectomy specimens: prevalence and association with BRCA germline mutation status. Am. J. Surg. Pathol. 2001;25:1283–1289
  63. Creasman WT, Odicino F, Maisonneuve P, Beller U, Benedet JL, Heintz AP, et al. Carcinoma of the corpus uteri. Int. J. Gynaecol. Obstet. 2003;83(Suppl. 1):79–118
  64. Crijnen ThEM, Janssen-Heijnen MLG, Gelderblom H, Morreau J, Nooij MA, Kenter GG, et al. Survival of patients with ovarian cancer due to a mismatch repair defect. Fam. Cancer. 2005;4:301–305
  65. Crum CP, Drapkin R, Kindelberger D, Drapkin R, Miron A, Ince TA, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr. Opin. Obstet. Gynecol. 2007;19:3–9
  66. Crum CP, Drapkin R, Kindelberger D, Medeiros F, Miron A, Lee Y. Lessons from BRCA: the tubal fimbria emerges as an origin for pelvic serous cancer. Clin. Med. Res. 2007;5:35–44
  67. Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet. 2003;361:296–300
  68. Das Gupta R, Kolodner RD. Novel dominant mutations in Saccharomyces cerevisiae MSH6. Nat. Genet. 2000;24:53–56
  69. Desai DC, Lockman JC, Chadwick RB, Gao X, Percesepe A, Evans DGR, et al. Recurrent germline mutation in MSH2 arises frequently de novo. J. Med. Genet. 2000;37:646–652
  70. Dorum A, Heimdal K, Lovslett K, Kristensen G, Hansen LJ, Sandvei R, et al. Prospectively detected cancer in familial breast/ovarian cancer screening. Acta Obstet. Gynecol. Scand. 1999;78:906–911
  71. Dove-Edwin I, Boks D, Goff S, Kenter GG, Carpenter R, Vasen HFA, et al. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer. 2002;94:1708–1712
  72. Drummond JT, Li G-M, Longley MJ, Modrich P. Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells. Science. 1995;268:1909–1912
  73. Dunlop MG, Farrington SM, Carothers AD, Wyllie AH, Sharp L, Burn J, et al. Cancer risk associated with germline DNA mismatch repair gene mutations. Hum. Mol. Genet. 1997;6:105–110
  74. Easton DF, Bishop DT, Ford D, Crockford GP, The Breast Cancer Linkage Consortium . Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am. J. Hum. Genet. 1993;52:678–701
  75. Easton DF, Ford D, Bishop DT, The Breast Cancer Linkage Consortium . Breast and ovarian cancer incidence in BRCA1 mutation carriers. Am. J. Hum. Genet. 1995;56:265–271
  76. Easton DF, Steele L, Fields P, Ormiston W, Averill D, Daly PA, et al. Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12–13. Am. J. Hum. Genet. 1997;61:120–128
  77. Eisen A, Lubinski J, Klijn J, Moller P, Lynch HT, Offit K, et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case–control study. J. Clin. Oncol. 2005;23:7491–7496
  78. Elie C, Geay JF, Morcos M, Le Tourneau A, Girre V, Broët P, et al. Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO Group). Br. J. Cancer. 2004;91:470–475
  79. Eltabbakh GH, Piver MS, Hempling RE, Recio FO, Paczos T. Laparoscopic management of women with a family history of ovarian cancer. J. Surg. Oncol. 1999;72:9–13
  80. Eshleman JR, Lang EZ, Bowerfind GK, Parsons R, Vogelstein B, Willson JK, et al. Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer. Oncogene. 1995;10:33–37
  81. Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J. Natl. Cancer Inst. 2000;92:564–569
  82. Fathalla MF. Incessant ovulation – a factor in ovarian neoplasia?. Lancet. 1971;ii(7716):163
  83. Feeley KM, Wells M. Hormone replacement therapy and the endometrium. J. Clin. Pathol. 2001;54:435–440
  84. Fishel R, Lescoe MK, Rao MRS, Copeland NG, Jenkins NA, Garber J, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993;75:1027–1038
  85. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl. Cancer Inst. 1998;90:1371–1388
  86. Fishman DA, Cohen L, Blank SV, Shulman L, Singh D, Bozorgi K, et al. The role of ultrasound evaluation in the detection of early-stage epithelial ovarian cancer. Am. J. Obstet. Gynecol. 2005;192:1214–1221
  87. Folkins AK, Jarboe EA, Saleemuddin A, Lee Y, Callahan MJ, Drapkin R, et al. A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations. Gynecol. Oncol. 2008;109:168–173
  88. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, Breast Cancer Linkage Consortium . Risks of cancer in BRCA1-mutation carriers. Lancet. 1994;343:692–695
  89. Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am. J. Hum. Genet. 1995;57:1457–1462
  90. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am. J. Hum. Genet. 1998;62:676–689
  91. Foulkes WD, Thiffault I, Gruber SB, Horwitz M, Hamel N, Lee C, et al. The founder mutation MSH2*1906GC is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population. Am. J. Hum. Genet. 2002;71:1395–1412
  92. Fraumeni JF, Grundy GW, Creagan ET, Everson RB. Six families prone to ovarian cancer. Cancer. 1975;36:364–369
  93. Friedman LS, Szabo CI, Ostermeyer EA, Dowd P, Butler L, Park T, et al. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families. Am. J. Hum. Genet. 1995;57:1284–1297
  94. Fujita M, Enomoto T, Yoshino K, Nomura T, Buzard GS, Inoue M, et al. Microsatellite instability and alterations in the hMSH2 gene in human ovarian cancer. Int. J. Cancer (Pred. Oncol.). 1995;64:361–366
  95. Gaarenstroom KN, van der Hiel B, Tollenaar RAEM, Vink GR, Jansen FW, van Asperen CJ, et al. Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study. Int. J. Gynecol. Cancer. 2006;16(Suppl. 1):54–59
  96. Gamallo C, Palacios J, Moreno G, Calvo de Mora J, Suárez A, Armas A. β-Catenin expression pattern in stage I and II ovarian carcinomas: relationship with β-catenin gene mutations, clinicopathological features, and clinical outcome. Am. J. Pathol. 1999;155:527–536
  97. Gambrell RD. Estrogens, progestogens and endometrial cancer. J. Reprod. Med. 1977;18:301–316
  98. Gambrell RD, Bagnell CA, Greenblatt RB. Role of estrogens and progesterone in the etiology and prevention of endometrial cancer: review. Am. J. Obstet. Gynecol. 1983;146:696–707
  99. Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BAJ, et al. Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat. Genet. 1997;15:103–105
  100. Gayther SA, Warren W, Mazoyer S, Russell PA, Harrington PA, Chiano M, et al. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype–phenotype correlation. Nat. Genet. 1995;11:428–433
  101. Genschel J, Littman SJ, Drummond JT, Modrich P. Isolation of MutSβ from human cells and comparison of the mismatch repair specificities of MutSβ and MutSα. J. Biol. Chem. 1998;273:19895–19901
  102. Gotlieb WH, Chetrit A, Menczer J, Hirsh-Yechezkel G, Lubin F, Friedman E, et al. Demographic and genetic characteristics of patients with borderline ovarian tumors as compared to early stage invasive ovarian cancer. Gynecol. Oncol. 2005;97:780–783
  103. Gras E, Catasus L, Argüelles R, Moreno-Bueno G, Palacios J, Gamallo C, et al. Microsatellite instability, MLH-1 promoter hypermethylation, and frameshift mutations at coding mononucleotide repeat microsatellites in ovarian tumors. Cancer. 2001;92:2829–2836
  104. Gray LA, Barnes ML. Carcinoma of the ovary: a report of 106 cases: 1. A further effort at pathological differentiation. Ann. Surg. 1962;155:722–732
  105. Green RC, Narod SA, Morasse J, Young TL, Cox J, Fitzgerald GW, et al. Hereditary nonpolyposis colon cancer: analysis of linkage to 2p15–16 places the COCA1 locus telomeric to D2S123 and reveals genetic heterogeneity in seven Canadian families. Am. J. Hum. Genet. 1994;54:1067–1077
  106. Gronwald J, Cybulski C, Lubinski J, Narod SA. Phenocopies in breast cancer 1 (BRCA1) families: implications for genetic counseling. J. Med. Genet. 2007;44:e76
  107. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset breast cancer to chromosome 17q21. Science. 1990;250:1684–1689
  108. Han HJ, Yanagisawa A, Kato Y, Park JG, Nakamura Y. Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer. Cancer Res. 1993;53:5087–5089
  109. Hartley A, Rollason T, Spooner D. Clear cell carcinoma of the fimbria of the fallopian tube in a BRCA1 carrier undergoing prophylactic surgery. Clin. Oncol. (R. Coll. Radiol.). 2000;12:58–59
  110. Hébert-Blouin MN, Koufogianis V, Gillett P, Foulkes WD. Fallopian tube cancer in a BRCA1 mutation carrier: rapid development and failure of screening. Am. J. Obstet. Gynecol. 2002;186:53–54
  111. Hendriks YMC, Wagner A, Morreau H, Menko F, Stormorken A, Quehenberger F, et al. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology. 2004;127:17–25
  112. Hilton JL, Geisler JP, Rathe JA, Hattermann-Zogg M, DeYoung B, Buller RE. Inactivation of BRCA1 and BRCA2 in ovarian cancer. J. Natl. Cancer Inst. 2002;94:1396–1406
  113. Hornreich G, Beller U, Lavie O, Renbaum P, Cohen Y, Levy-Lahad E. Is uterine serous carcinoma a BRCA1-related disease? Case report and review of the literature. Gynecol. Oncol. 1999;75:300–304
  114. Huang J, Kuismanen SA, Liu T, Chadwick RB, Johnson CK, Stevens MW, et al. MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon cancer. Cancer Res. 2001;61:1619–1623
  115. Iaccarino I, Marra G, Palombo F, Jiricny J. hMSH2 and hMSH6 play distinct roles in mismatch binding and contribute differently to the ATPase activity of hMutSα. EMBO J. 1998;17:2677–2686
  116. Ionov YM, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363:558–561
  117. Jarboe E, Folkins A, Nucci MR, Kindelberger D, Drapkin R, Miron A, et al. Serous carcinogenesis in the fallopian tube: a descriptive classification. Int J Gynecol. Pathol. 2008;27:1–9
  118. Jarboe EA, Folkins AK, Drapkin R, Ince TA, Agoston ES, Crum CP. Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective. Histopathology. 2008;53:127–138
  119. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J. Clin. 2008;58:71–96
  120. Jick SS, Walker AM, Jick H. Estrogens, progesterone, and endometrial cancer. Epidemiology. 1993;4:20–24
  121. Johannesdottir G, Gudmundsson J, Bergthorsson JT, Arason A, Agnarsson BA, Eiriksdottir G, et al. High prevalence of the 999del5 mutation in Icelandic breast and ovarian cancer patients. Cancer Res. 1996;56:3663–3665
  122. Jóhannsson OT, Ranstam J, Borg A, Olsson H. Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden. J. Clin. Oncol. 1998;16:397–404
  123. Jongsma AP, Piek JM, Zweemer RP, Verheijen RH, Klein Gebbinck JW, van Kamp GJ, et al. Molecular evidence for putative tumour suppressor genes on chromosome 13q specific to BRCA1 related ovarian and fallopian tube cancer. Mol. Pathol. 2002;55:305–309
  124. Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, Garber JE, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J. Clin. Oncol. 2008;26:1331–1337
  125. Kauff ND, Hurley KE, Hensley ML, Robson ME, Lev G, Goldfrank D, et al. Ovarian carcinoma screening in women at intermediate risk: impact on quality of life and need for invasive follow-up. Cancer. 2005;104:314–320
  126. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N. Engl. J. Med. 2002;346:1609–1615
  127. Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am. J. Surg. Pathol. 2007;31:161–169
  128. King MC, Marks JH, Mandell JB New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302:643–646
  129. King MC, Wieand S, Hale K, Lee M, Walsh T, Owens K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) breast cancer prevention trial. JAMA. 2001;286:2251–2256
  130. Kobayashi H, Yamada Y, Sado T, Sakata M, Yoshida S, Kawaguchi R, et al. A randomized study of screening for ovarian cancer: a multicenter study from Japan. Int. J. Gynecol. Cancer. 2008;18:414–420
  131. Kohler MF, Kerns BJ, Humphrey PA, Marks JR, Bast RC, Berchuck A. Mutation and overexpression of p53 in early-stage epithelial ovarian cancer. Obstet. Gynecol. 1993;81:643–650
  132. Koi M, Umar A, Chauhan DP, Cherian SP, Carethers JM, Kunkel TA, et al. Human chromosome 3 corrects mismatch repair deficiency and microsatellite instability and reduces N-methyl-N′-nitro-N-nitrosoguanidine tolerance in colon tumor cells with homozygous hMLH1 mutation. Cancer Res. 1994;54:4308–4312
  133. Kong D, Suzuki A, Zou TT, Sakurada A, Kemp LW, Wakatsuki S. PTEN1 is frequently mutated in primary endometrial carcinomas. Nat. Genet. 1997;17:143–144
  134. Kringen P, Wang Y, Dumeaux V, Nesland JM, Kristensen G, Borresen-Dale AL, et al. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival. BMC Cancer. 2005;5:134
  135. Kuismanen SA, Moisio AL, Schweizer P, Truninger K, Salovaara R, Arola J, et al. Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability. Am. J. Pathol. 2002;160:1953–1958
  136. Kupryjanczyk J, Thor AD, Beauchamp R, Merritt V, Edgerton SM, Bell DA, et al. p53 Gene mutations and protein accumulation in human ovarian cancer. Proc. Natl. Acad. Sci. U.S.A. 1993;90:4961–4965
  137. Kurman RJ, Shih le M. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int. J. Gynecol. Pathol. 2008;27:151–160
  138. Kwon JS, Lenehan J, Carey M, Ainsworth P. Prolonged survival among women with BRCA germline mutations and advanced endometrial cancer: a case series. Int. J. Gynecol. Cancer. 2008;18:546–549
  139. Kwon JS, Sun CC, Peterson SK, White KG, Daniels MS, Boyd-Rogers SG, et al. Cost-effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome. Cancer. 2008;113:326–335
  140. Lacey JV, Brinton LA, Lubin JH, Sherman ME, Schatzkin A, Schairer C. Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women. Cancer Epidemiol. Biomarkers Prev. 2005;14:1724–1731
  141. Lafky JM, Wilken JA, Baron AT, Maihle NJ. Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. Biochim. Biophys. Acta. 2008;1785:232–265
  142. Laframboise S, Nedelcu R, Murphy J, Cole DE, Rosen B. Use of CA-125 and ultrasound in high-risk women. Int. J. Gynecol. Cancer. 2002;12:86–91
  143. Lakhani SR, Manek S, Penault-Llorca F, Flanagan A, Arnout L, Mettett S, et al. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers. Clin. Cancer Res. 2004;10:2473–2481
  144. Lamb JD, Garcia RL, Goff BA, Paley PJ, Swisher EM. Predictors of occult neoplasia in women undergoing risk-reducing salpingo-oophorectomy. Am. J. Obstet. Gynecol. 2006;194:1702–1709
  145. Landen CN, Birrer MJ, Sood AK. Early events in the pathogenesis of epithelial ovarian cancer. J. Clin. Oncol. 2008;26:995–1005
  146. Lauchlan SC. The secondary mullerian system. Obstet. Gynecol. Surv. 1972;27:133–146
  147. Lavie O, Hornreich G, Ben-Arie A, Rennert G, Cohen Y, Keidar R, et al. BRCA germline mutations in Jewish women with uterine serous papillary carcinoma. Gynecol. Oncol. 2004;92:521–524
  148. Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993;75:1215–1225
  149. Lee Y, Medeiros F, Kindelberger D, Callahan MJ, Muto MG, Crum CP. Advances in the recognition of tubal intraepithelial carcinoma: applications to cancer screening and the pathogenesis of ovarian cancer. Adv. Anat. Pathol. 2006;13:1–7
  150. Lee Y, Miron A, Drapkin R, Nucci MR, Medeiros F, Saleemuddin A, et al. A candidate precursor to serous carcinoma that originates in the distal fallopian tube. J. Pathol. 2007;211:26–35
  151. Leeper L, Garcia R, Swisher E, Goff B, Greer B, Paley P. Pathologic findings in prophylactic oophorectomy specimens in high-risk women. Gynecol. Oncol. 2002;87:52–56
  152. Levanon K, Crum C, Drapkin R. New insights into the pathogenesis of serous ovarian cancer and its clinical impact. J. Clin. Oncol. 2008;26:5284–5293
  153. Levine DA, Argenta PA, Yee CJ, Marshall DS, Olvera N, Bogomolniy F, et al. Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations. J. Clin. Oncol. 2003;21:4222–4227
  154. Levine DA, Lin O, Barakat RR, Robson ME, McDermott D, Cohen L, et al. Risk of endometrial carcinoma associated with BRCA mutation. Gynecol. Oncol. 2001;80:395–398
  155. Levine RL, Cargile CB, Blazes MS, van Rees B, Kurman RJ, Ellenson LH. PTEN mutations and microsatellite instability in complex atypical hyperplasia, a precursor lesion to uterine endometrioid carcinoma. Cancer Res. 1998;58:3254–3258
  156. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–1947
  157. Liede A, Karlan BY, Baldwin RL, Platt LD, Kuperstein G, Narod SA. Cancer incidence in a population of Jewish women at risk of ovarian cancer. J. Clin. Oncol. 2002;20:1570–1577
  158. Lindblom A, Tannergard P, Werelius B, Nordenskjold M. Genetic mapping of a second locus predisposing to hereditary nonpolyposis colorectal cancer. Nat. Genet. 1993;5:279–282
  159. Liu B, Parsons R, Papadopoulos N, Nicolaides NC, Lynch HT, Watson P, et al. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat. Med. 1996;2:169–174
  160. Liu J, Albarracin CT, Chang K-H, Thompson-Lanza JA, Zheng W, Gershenson DM, et al. Microsatellite instability and expression of hMLH1 and hMSH2 proteins in ovarian endometrioid cancer. Mod. Pathol. 2004;17:75–80
  161. Lu KH. Hereditary gynecologic cancers: differential diagnosis, surveillance, management and surgical prophylaxis. Fam. Cancer. 2008;7:53–58
  162. Lu KH, Cramer DW, Muto MG, Li EY, Niloff J, Mok SC. A population-based study of BRCA1 and BRCA2 mutations in Jewish women with epithelial ovarian cancer. Obstet. Gynecol. 1999;93:34–37
  163. Lubinski J, Phelan CM, Ghadirian P, Lynch HT, Garber J, Weber B, et al. Cancer variation associated with the position of the mutation in the BRCA2 gene. Fam. Cancer. 2004;3:1–10
  164. Lynch HT, Bewtra C, Lynch JF. Familial peritoneal ovarian carcinomatosis: a new clinical entity?. Med. Hypoth. 1986;21:171–177
  165. Lynch HT, Boland CR, Gong G, Shaw TG, Lynch PM, Fodde R, et al. Phenotypic and genotypic heterogeneity in the Lynch syndrome: diagnostic, surveillance and management implications. Eur. J. Hum. Genet. 2006;14:390–402
  166. Lynch HT, Casey MJ. Prophylactic surgery prevents endometrial and ovarian cancer in the Lynch syndrome. Nat. Clin. Pract. Oncol. 2007;4:672–673
  167. Lynch HT, Casey MJ, Lynch J, White TEK, Godwin AK. Genetics and ovarian carcinoma. Sem. Oncol. 1998;25:265–281
  168. Lynch HT, Cavalieri RJ, Lynch JF, Casey MJ. Gynecologic clues to Lynch syndrome II diagnosis: a family report. Gynecol. Oncol. 1992;44:198–203
  169. Lynch HT, Coronel SM, Okimoto R, Hampel H, Sweet K, Lynch JF, et al. A founder mutation of the MSH2 gene and hereditary nonpolyposis colorectal cancer in the United States. JAMA. 2004;291:718–724
  170. Lynch HT, de la Chapelle A. Genetic susceptibility to non-polyposis colorectal cancer. J. Med. Genet. 1999;36:801–818
  171. Lynch HT, de la Chapelle A, Hampel H, Wagner A, Fodde R, Lynch JF, et al. The American founder mutation for Lynch syndrome: prevalence estimates and implications. Cancer. 2006;106:448–452
  172. Lynch HT, Guirgis HA, Albert S, Brennan M, Lynch J, Kraft C, et al. Familial association of carcinoma of the breast and ovary. Surg. Gynecol. Obstet. 1974;138:717–724
  173. Lynch HT, Krush AJ. Heredity and adenocarcinoma of the colon. Gastroenterology. 1967;53:517–527
  174. Lynch HT, Krush AJ. Carcinoma of the breast and ovary in three families. Surg. Gynecol. Obstet. 1971;133:644–648
  175. Lynch HT, Krush AJ, Lemon HM, Kaplan AR, Condit PT, Bottomley RH. Tumor variation in families with breast cancer. JAMA. 1972;222:1631–1635
  176. Lynch HT, Lynch JF, Lynch PM, Attard T. Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam. Cancer. 2008;7:27–39
  177. Lynch HT, Lynch PM. The cancer-family syndrome: a pragmatic basis for syndrome identification. Dis. Colon Rectum. 1979;22:106–110
  178. Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ. Hereditary factors in cancer: study of two large Midwestern kindreds. Arch. Intern. Med. 1966;117:206–212
  179. Mæhle L, Apold J, Paulsen T, Hagen B, Løvslett K, Fiane B, et al. High risk for ovarian cancer in a prospective series is restricted to BRCA1/2 mutation carriers. Clin. Cancer Res. 2008;14:7569–7573
  180. Maihle NJ, Baron AT, Barrette BA, Boardman CH, Christensen TA, Cora EM, et al. EGF/ErbB receptor family in ovarian cancer. Cancer Treat. Res. 2002;107:247–258
  181. Malander S, Rambech E, Kristoffersson U, Halvarsson B, Ridderheim M, Borg Å, et al. The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer. Gynecol. Oncol. 2006;101:238–243
  182. Malkhosyan S, Rampino N, Yamamoto H, Perucho M. Frameshift mutator mutations. Nature. 1996;382:499–500
  183. Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, et al. Grading ovarian serous carcinoma using a two-tier system. Am. J. Surg. Pathol. 2004;28:496–504
  184. Marsischky GT, Filosi N, Kane MF, Kolodner R. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev. 1996;10:407–420
  185. Martini M, Ciccarone M, Garganese G, Maggiore C, Evangelista A, Rahimi S, et al. Possible involvement of the hMLH1, p16INK4a and PTEN in the malignant transformation of endometriosis. Int. J. Cancer. 2002;102:398–406
  186. Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, et al. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J. Natl. Cancer Inst. 2004;96:1751–1761
  187. Matsuyama Y, Tominaga T, Nomura Y, Koyama H, Kimura M, Sano M, et al. Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan. Ann. Oncol. 2000;11:1537–1543
  188. Maxwell GL, Risinger JI, Gumbs C, Shaw H, Bentley RC, Barrett JC. Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias. Cancer Res. 1998;58:2500–2503
  189. Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am. J. Surg. Pathol. 2006;30:230–236
  190. Meeuwissen PA, Seynaeve C, Brekelmans CT, Meijers-Heijboer HJ, Klijn JG, Burger CW. Outcome of surveillance and prophylactic salpingo-oophorectomy in asymptomatic women at high risk for ovarian cancer. Gynecol. Oncol. 2005;97:476–482
  191. Merajver SD, Pham TM, Caduff RF, Chen M, Poy EL, Cooney KA, et al. Somatic mutations in the BRCA1 gene in sporadic ovarian tumours. Nat. Genet. 1995;9:439–443
  192. Mignotte H, Lasset C, Bonadona V, Lesur A, Luporsi E, Rodier J-F, et al. Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case–control study. Int. J. Cancer. 1998;76:325–330
  193. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266:66–71
  194. Milne RL, Osorio A, Cajal TR, Vega A, Llort G, de la Hoya M, et al. The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain. Clin. Cancer Res. 2008;14:2861–2869
  195. Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, et al. Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat. Genet. 1997;17:271–272
  196. Moisio A-L, Sistonen P, Weissenbach J, de la Chapelle A, Peltomaki P. Age and origin of two common MLH1 mutations predisposing to hereditary colon cancer. Am. J. Hum. Genet. 1996;59:1243–1251
  197. Mok SC, Bell DA, Knapp RC, Fishbaugh PM, Welch WR, Muto MG, et al. Mutation of K-ras protooncogene in human ovarian epithelial tumors of borderline malignancy. Cancer Res. 1993;53:1489–1492
  198. Morice P, Mercier S, Spatz A, L'homme C, Duvillard P, Gerbault A, et al. Laparoscopic prophylactic oophorectomy in women with inherited risk of ovarian cancer. Eur. J. Gynaecol. Oncol. 1999;20:202–204
  199. Mutter GL, Lin M-C, Fitzgerald JT, Kum JB, Baak JPA, Lees JA, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J. Natl. Cancer Inst. 2000;92:924–931
  200. Myrhoj T, Bisgaard ML, Bernstein I, Svendsen LB, Sondergaard JO, Bülow S. Hereditary non-polyposis colorectal cancer: clinical features and survival: results from the Danish HNPCC Register. Scand. J. Gastroenterol. 1997;32:572–576
  201. Nakagawa H, Lockman JC, Frankel WL, Hampel H, Steenblock K, Burgart LJ, et al. Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Cancer Res. 2004;64:4721–4727
  202. Nakayama K, Nakayama N, Kurman RJ, Cope L, Pohl G, Samuels Y, et al. Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms. Cancer Biol. Ther. 2006;5:779–785
  203. Narod S, Ford D, Devilee P, Barkardottir RB, Eyfjord J, Lenoir G, et al. Genetic heterogeneity of breast–ovarian cancer revisited. Am. J. Hum. Genet. 1995;57:957–958
  204. Narod SA, Brunet J-S, Ghadirian P, Robson M, Heimdal K, Neuhausen SL, et al. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case–control study. Lancet. 2000;356:1876–1881
  205. Narod SA, Feunteun J, Lynch HT, Watson P, Conway T, Lenoir GM. Familial breast–ovarian cancer locus on chromosome 17q12–q23. Lancet. 1991;388:82–83
  206. Narod SA, Ford D, Devilee P, Barkardottir RB, Lynch HT, Smith SA, et al. An evaluation of genetic heterogeneity in 145 breast–ovarian cancer families. Am. J. Hum. Genet. 1995;56:254–264
  207. National Center for Biotechnology Information . Gene. National Institutes of Health; 2008;Available at: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene(Accessed on 21 January 2009)
  208. Newcomb PA, Trentham-Dietz A. Patterns of postmenopausal progestin use with estrogen in relation to endometrial cancer (United States). Cancer Causes Control. 2003;14:195–201
  209. Nicolaides NC, Papadopoulos N, Liu B, Wei Y-F, Carter KC, Ruben SM, et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994;371:75–80
  210. Nyström-Lahti M, Kristo P, Nicolaides NC, Chang SY, Aaltonen LA, Moisio A-L, et al. Founding mutations and Alu-mediated recombination in hereditary colon cancer. Nat. Med. 1995;1:1203–1206
  211. Nyström-Lahti M, Sistonen P, Mecklin J-P, Pylkkänen L, Aaltonen LA, Järvinen H, et al. Close linkage to chromosome 3p and conservation of ancestral founding haplotype in hereditary nonpolyposis colorectal cancer families. Proc. Natl. Acad. Sci. U.S.A. 1994;91:6054–6058
  212. Nyström-Lahti M, Wu Y, Moisio A-L, Hofstra RMW, Osinga J, Mecklin J-P, et al. DNA mismatch repair gene mutations in 55 kindreds with verified or putative hereditary nonpolyposis colorectal cancer. Hum. Mol. Genet. 1996;5:763–769
  213. Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ, et al. Frequent PTEN/MMAC1 mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res. 1998;58:2095–2097
  214. Oei AL, Massuger LF, Bulten J, Ligtenberg MJ, Hoogerbrugge N, de Hullu JA. Surveillance of women at high risk for hereditary ovarian cancer is inefficient. Br. J. Cancer. 2006;94:814–819
  215. Olivier RI, Lubsen-Brandsma MA, Verhoef S, van Beurden M. CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol. Oncol. 2006;100:20–26
  216. Olivier RI, van Beurden M, Lubsen MA, Rookus MA, Mooij TM, van de Vijver MJ, et al. Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up. Br. J. Cancer. 2004;90:1492–1497
  217. Osborne RJ, Leech V. Polymerase chain reaction allelotyping of human ovarian cancer. Br. J. Cancer. 1994;69:429–438
  218. Ozols RF, Rubin SC, Thomas GM, Robboy SJ. Epithelial ovarian cancer. In:  Hoskins WJ,  Perez CA,  Young RC,  Barakat RR,  Markman M,  Randall ME editor. Principles and Practice of Gynecologic Oncology. fifth ed.. Philadelphia, PA: Lippincott Williams & Wilkins; 2005;p. 903–904
  219. Pal T, Permuth-Wey J, Kapoor R, Cantor A, Sutphen R. Improved survival in BRCA2 carriers with ovarian cancer. Fam. Cancer. 2007;6:113–119
  220. Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005;104:2807–2816
  221. Pal T, Permuth-Wey J, Kumar A, Sellers TA. Systematic review and meta-analysis of ovarian cancers: estimation of microsatellite-high frequency and characterization of mismatch repair deficient tumor histology. Clin. Cancer Res. 2008;14:6847–6854
  222. Pal T, Permuth-Wey J, Sellers TA. A review of the clinical relevance of mismatch-repair deficiency in ovarian cancer. Cancer. 2008;113:733–742
  223. Paley PJ, Swisher EM, Garcia RL, Agoff SN, Greer BE, Peters KL, et al. Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy as surgical prophylaxis. Gynecol. Oncol. 2001;80:176–180
  224. Palombo F, Gillinari P, Iaccarino I, Lettieri T, Hughes M, D'Arrigo A, et al. GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells. Science. 1995;268:1912–1914
  225. Papadopoulos N, Nicolaides NC, Wei Y-F, Ruben SM, Carter KC, Rosen CA, et al. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994;263:1625–1629
  226. Parmley TH, Woodruff JD. The ovarian mesothelioma. Am. J. Obstet. Gynecol. 1974;120:234–241
  227. Patai K, Szentmariay F, Jakab Z, Szilagyi G. Early detection of endometrial cancer by combined use of vaginal ultrasound and endometrial vacuum sampling. Int. J. Gynecol. Cancer. 2002;12:261–264
  228. Peiffer SL, Herzog TJ, Tribune DJ, Mutch DG, Gersell DJ, Goodfellow PJ. Allelic loss of sequences from the long arm of chromosome 10 and replication errors in endometrial cancers. Cancer Res. 1995;55:1922–1926
  229. Peltomäki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J. Clin. Oncol. 2003;21:1174–1179
  230. Peltomäki P, Aaltonen L, Sistonen P, Pylkkänen L, Mecklin J-P, Järvinen H, et al. Genetic mapping of a locus predisposing to human colorectal cancer. Science. 1993;260:810–812
  231. Peltomäki P, Vasen H. Mutations associated with HNPCC predisposition – update of ICG-HNPCC/INSiGHT mutation database. Dis. Markers. 2004;20:269–276
  232. Peltomäki P, Vasen HFA International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. Gastroenterology. 1997;113:1146–1158
  233. Peters-Engl C, Frank W, Danmayr E, Friedl HP, Leodolter S, Medl M. Association between endometrial cancer and tamoxifen treatment of breast cancer. Breast Cancer. Res. Treat. 1999;54:255–260
  234. Peyton-Jones B, Olaitan A, Murdoch JB. Incidental diagnosis of primary fallopian tube carcinoma during prophylactic salpingo-oophorectomy. BJOG. 2002;109:1413–1414
  235. Pharoah PD, Easton DF, Stockton DL, Gayther S, Ponder BA. Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group. Cancer Res. 1999;59:868–871
  236. Piek J, Kenemans P, Verheijen R. Intraperitoneal serous adenocarcinoma: a critical appraisal of three hypotheses on its cause. Am. J. Obstet. Gynecol. 2004;191:718–732
  237. Piek JM, Torrenga B, Hermsen B, Verheijen RH, Zweemer RP, Gille JJ, et al. Histopathological characteristics of BRCA1- and BRCA2-associated intraperitoneal cancer: a clinic-based study. Fam. Cancer. 2003;2:73–78
  238. Piek JM, Verheijen RH, Menko FH, Jongsma AP, Weegenaar J, Gille JJ, et al. Expression of differentiation and proliferation related proteins in epithelium of prophylactically removed ovaries from women with a hereditary female adnexal cancer predisposition. Histopathology. 2003;43:26–32
  239. Piver MS, Goldberg JM, Tsukada Y, Mettlin CJ, Jiski MG, Natardjen N. Characteristics of familial ovarian cancer: a report of the first 1,000 families in the Gilda Radner Familial Ovarian Cancer Registry. Eur. J. Gynecol. Oncol. 1996;17:169–176
  240. Plaschke J, Krüger S, Jeske B, Theissig F, Kreuz FR, Pistorius S, et al. Loss of MSH3 protein expression is frequent in MLH1-deficient colorectal cancer and is associated with disease progression. Cancer Res. 2004;64:864–870
  241. Powell CB. Occult ovarian cancer at the time of risk-reducing salpingo-oophorectomy. Gynecol. Oncol. 2006;100:1–2
  242. Powell CB, Kenley E, Chen LM, Crawford B, McLennan J, Zaloudek C, et al. Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J. Clin. Oncol. 2005;23:127–132
  243. Pukkla E, Kyyronen P, Sankila R, Holli K. Tamoxifen and toremifen treatment of breast cancer and risk of subsequent endometrial cancer: a population-based case–control study. Int. J. Cancer. 2002;100:337–341
  244. Quehenberger F, Vasen HF, van Houwelingen HC. Risk of colorectal and endometrial cancer for carriers of mutations of the hMLH1 and hMSH2 gene: correction for ascertainment. J. Med. Genet. 2005;42:491–496
  245. Rafnar T, Benediktsdottir KR, Eldon BJ, Gestsson T, Saemundsson H, Olafsson K, et al. BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. Eur. J. Cancer. 2004;40:2788–2793
  246. Ramus SJ, Fishman A, Pharoah PD, Yarkoni S, Altaras M, Ponder BA. Ovarian cancer survival in Ashkenazi Jewish patients with BRCA1 and BRCA2 mutations. Eur. J. Surg. Oncol. 2001;27:278–281
  247. Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J. Clin. Oncol. 2005;23:7804–7810
  248. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, van't Veer L, Garber JE, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N. Engl. J. Med. 2002;346:1616–1622
  249. Renkonen-Sinisalo L, Butzow R, Leminen A, Lehtovirta P, Mecklin JP, Järvinen HJ. Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome. Int. J. Cancer. 2006;120:821–824
  250. Ricciardone MD, Özçelik T, Cevher B, Özdag H, Tuncer M, Gürgey A, et al. Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type I. Cancer Res. 1999;59:290–293
  251. Rijcken FEM, Mourits MJE, Kleibeuker JH, Hollema H, van der Zee AGJ. Gynecologic screening in hereditary nonpolyposis colorectal cancer. Gynecol. Oncol. 2003;91:74–80
  252. Risinger JI, Hayes AK, Berchuck A, Barrett JC. PTEN/MMAC1 mutations in endometrial cancers. Cancer Res. 1997;57:4736–4738
  253. Rose PG, Shrigley R, Siesner GL. Germline BRCA2 mutation in a patient with fallopian tube carcinoma: a case report. Gynecol. Oncol. 2000;77:319–320
  254. Rosen DG, Cai KQ, Luthra R, Liu J. Immunohistochemical staining of hMLH1 and hMSH2 reflects microsatellite instability status in ovarian carcinoma. Modern Pathol. 2006;19:1414–1420
  255. Rubin SC, Benjamin I, Behbakht K, Takahashi H, Morgan MA, LiVolsi VA, et al. Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1. N. Engl. J. Med. 1996;335:1413–1416
  256. Rubin SC, Blackwood MA, Bandera C, Behbakht K, Benjamin I, Rebbeck TR, et al. BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. Am. J. Obstet. Gynecol. 1998;178:670–677
  257. Rutter JL, Wacholder S, Chetrit A, Lubin F, Menczer J, Ebbers S, et al. Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case–control study. J. Natl. Cancer Inst. 2003;95:1072–1078
  258. Sakurada A, Hamada H, Fukushige S, Yokoyama T, Yoshinaga K, Furukawa T, et al. Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer. Int. J. Oncol. 1999;15:1069–1074
  259. Salazar H, Godwin AK, Daly MB, Laub PB, Hogan WM, Rosenblum N, et al. Microscopic benign and invasive malignant neoplasms and a cancer-prone phenotype in prophylactic oophorectomies. J. Natl. Cancer Inst. 1996;88:1810–1820
  260. Salovaara R, Loukola A, Kristo P, Kääriäinen H, Ahtola H, Eskelinen M, et al. Population-based molecular detection of hereditary nonpolyposis colorectal cancer. J. Clin. Oncol. 2000;18:2193–2200
  261. Sarrió D, Moreno-Bueno G, Sánchez-Estévez C, Bañón-Rodriguez I, Hernández-Cortés G, Hardisson D, et al. Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas. Hum. Pathol. 2006;37:1042–1049
  262. Satagopan JM, Boyd J, Kauff ND, Robson M, Scheuer L, Narod S, et al. Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2. Clin. Cancer Res. 2002;8:3776–3781
  263. Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T, et al. Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res. 2000;60:7052–7056
  264. Scambia G, Benedetti Panici P, Battaglia F, Ferrandina G, Baiocchi G, Greggi S, et al. Significance of epidermal growth factor receptor in advanced ovarian carcinoma. J. Clin. Oncol. 1992;10:529–535
  265. Scheuer L, Kauff N, Robson M, Kelly B, Barakat R, Satagopan J, et al. Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J. Clin. Oncol. 2002;20:1260–1268
  266. Schmeler KM, Lynch HT, Chen L-M, Munsell MF, Soliman PT, Clark MB, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N. Engl. J. Med. 2006;354:261–269
  267. Schmutte C, Marinescu RC, Copeland NG, Jenkins NA, Overhauser J, Fishel R. Refined chromosomal localization of the mismatch repair and hereditary nonpolyposis colorectal cancer genes hMSH2 and hMSH6. Cancer Res. 1998;58:5023–5026
  268. Schubert EL, Lee MK, Mefford HC, Argonza RH, Morrow JE, Hull J, et al. BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2. Am. J. Hum. Genet. 1997;60:1031–1040
  269. Schweizer P, Moisio AL, Kuismanen SA, Truninger K, Vierumaki R, Salovaara R, et al. Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in hereditary nonpolyposis colorectal cancer. Cancer Res. 2001;61:2813–2815
  270. Seidman JD, Russell P, Kurman RJ. Surface epithelial tumors of the ovary. In:  Kurman RJ editors. Blaustein's Pathology of Ovarian Cancer. fifth ed.. New York: Springer Publishers; 2002;p. 791–805
  271. Shaw PA, McLaughlin JR, Zweemer RP, Narod SA, Risch H, Verheijen RH, et al. Histopathologic features of genetically determined ovarian cancer. Int. J. Gynecol. Pathol. 2002;21:407–411
  272. Shelly W, Draper MW, Krishman V. Selective estrogen receptor modulator: an update on recent clinical findings. Obstet. Gynecol. Surv. 2008;63:163–181
  273. Shih le M, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am. J. Pathol. 2004;164:1511–1518
  274. Simard J, Tonin P, Durocher F, Morgan K, Rommens J, Gingras S, et al. Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat. Genet. 1994;8:392–398
  275. Singer G, Oldt R, Cohen Y, Wang BG, Sidransky D, Kurman RJ, et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J. Natl. Cancer Inst. 2003;95:484–486
  276. Singer G, Shih I-M, Truskinovsky A, Umudum H, Kurman RJ. Mutational analysis of K-ras segregates ovarian serous carcinomas into two types: invasive MPSC (low-grade tumor) and conventional serous carcinoma (high-grade tumor). Int. J. Gynecol. Pathol. 2003;22:37–41
  277. Singer G, Stöhr R, Cope L, Dehari R, Hartmann A, Cao DF, et al. Patterns of p53 mutations separate ovarian serous borderline tumors and low- and high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: a mutational analysis with immunohistochemical correlation. Am. J. Surg. Pathol. 2005;29:218–224
  278. Skilling JS, Sood A, Niemann T, Lager DJ, Buller RE. An abundance of p53 null mutations in ovarian carcinoma. Oncogene. 1996;13:117–123
  279. Smith A, Moran A, Boyd MC, Bulman M, Shenton A, Smith L, et al. Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening. J. Med. Genet. 2007;44:10–15
  280. Soegaard M, Kjaer SK, Cox M, Wozniak E, Høgdall E, Høgdall C, et al. BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark. Clin. Cancer Res. 2008;14:3761–3767
  281. Sood AK, Holmes R, Hendrix MJ, Buller RE. Application of the National Cancer Institute international criteria for determination of microsatellite instability in ovarian cancer. Cancer Res. 2001;61:4371–4374
  282. Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N. Engl. J. Med. 1997;336:1401–1408
  283. Struewing JP, Watson P, Easton DF, Ponder BAJ, Lynch HT, Tucker MA. Prophylactic oophorectomy in inherited breast/ovarian cancer families. J. Natl. Cancer Inst. Monogr. 1995;17:33–35
  284. Sun S, Greenwood CM, Thiffault I, Hamel N, Chong G, Foulkes WD. The HNPCC associated MSH2*1906GC founder mutation probably originated between 1440 CE and 1715 CE in this Ashkenazi Jewish population. J. Med. Genet. 2005;42:766–768
  285. Tailor A, Bourne TH, Campbell S, Okokon E, Dew T, Collins WP. Results from an ultrasound-based familial ovarian cancer screening clinic: a 10-year observational study. Ultrasound Obstet. Gynecol. 2003;21:378–385
  286. Tan DS, Rothermundt C, Thomas K, Bancroft E, Eeles R, Shanley S, et al. “BRCAness” syndrome in ovarian cancer: a case–control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations. J. Clin. Oncol. 2008;26:5530–5536
  287. Tannergård PM, Zabarovsky E, Stanbridge E, Nordenskjöld M, Lindblom A. Sublocalization of a locus at 3-21.3-23 predisposing to hereditary nonpolyposis colon cancer. Hum. Genet. 1994;94:210–214
  288. Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res. 1997;57:3935–3940
  289. Teneriello MG, Ebina M, Linnoila RI, Henry M, Nash JD, Park RC, et al. p53 and Ki-ras gene mutations in epithelial ovarian neoplasms. Cancer Res. 1993;53:3103–3108
  290. The Anglian Breast Cancer Study Group . Prevalence of BRCA1 and BRCA2 mutations in a large population based series of breast cancer cases. Br. J. Cancer. 2000;83:1301–1308
  291. The Breast Cancer Linkage Consortium . Cancer risks in BRCA2 mutation carriers. J. Natl. Cancer Inst. 1999;91:1310–1316
  292. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816–819
  293. Thompson D, Easton D, Breast Cancer Linkage Consortium . Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am. J. Hum. Genet. 2001;68:410–419
  294. Thompson D, Easton D, Breast Cancer Linkage Consortium . Variation in BRCA1 cancer risks by mutation position. Cancer Epidemiol. Biomarkers Prev. 2002;11:329–336
  295. Thompson D, Easton DF, Breast Cancer Linkage Consortium . Cancer incidence in BRCA1 mutation carriers. J. Natl. Cancer Inst. 2002;94:1358–1365
  296. Tobias DH, Eng C, McCurdy LD, Kalir T, Mandelli J, Dottino PR, et al. Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish ovarian cancer patients. Gynecol. Oncol. 2000;78:148–151
  297. Tong D, Stimpfl M, Reinthaller A, Vavra N, Müllauer-Ertl S, Leodolter S, et al. BRCA1 gene mutations in sporadic ovarian carcinomas: detection by PCR and reverse allele-specific oligonucleotide hybridization. Clin. Chem. 1999;45:976–981
  298. Tonin P, Moslehi R, Green R, Rosen B, Cole D, Boyd N, et al. Linkage analysis of 26 Canadian breast and breast–ovarian cancer families. Hum. Genet. 1995;95:545–550
  299. Tulinius H, Olafsdottir GH, Sigvaldason H, Arason A, Barkardottir RB, Egilsson V, et al. The effect of a single BRCA2 mutation on cancer in Iceland. J. Med. Genet. 2002;39:457–462
  300. Ursic-Vrscaj M, Kovacic J, Bebar S, Djurisic A, Fras PA, Robie V. Endometrial and other primary cancers after tamoxifen treatment of breast cancer – results of retrospective cohort study. Eur. J. Obstet. Gynecol. Reprod. Biol. 2001;95:105–110
  301. van der Klift H, Wijnen J, Wagner A, Verkuilen P, Tops C, Otway R, et al. Molecular characterization of the spectrum of genomic deletions in the mismatch repair genes MSH2, MLH1, MSH6, and PMS2 responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Genes Chromosomes Cancer. 2005;44:123–138
  302. van Nagell JR, DePriest PD, Reedy MB, Gallion HH, Ueland FR, Pavlik EJ, et al. The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer. Gynecol. Oncol. 2000;77:350–356
  303. Vasen HF, Tesfay E, Boonstra H, Mourits MJ, Rutgers E, Verheyen R, et al. Early detection of breast and ovarian cancer in families with BRCA mutations. Eur. J. Cancer. 2005;41:549–554
  304. Vasen HFA, Stormorken A, Menko FH, Nagengast FM, Kleibeuker JH, Griffioen G, et al. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J. Clin. Oncol. 2001;19:4074–4080
  305. Vasen HFA, Watson P, Mecklin J-P, Lynch HT, Icg-Hnpcc . New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology. 1999;116:1453–1456
  306. Vasen HFA, Wijnen JT, Menko FH, Kleibeuker JH, Taal BG, Griffioen G, et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology. 1996;110:1020–1027
  307. Vilkki S, Tsao J-L, Loukola A, Pöyhönen M, Vierimaa O, Herva R, et al. Extensive somatic microsatellite mutations in normal human tissue. Cancer Res. 2001;61:4541–4544
  308. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat. Rev. Cancer. 2002;2:489–501
  309. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006;295:2727–2741
  310. Wagner A, Barrows A, Wijnen JT, van der Klift H, Franken PF, Verkuijlen P, et al. Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. Am. J. Hum. Genet. 2003;72:1088–1100
  311. Wagner A, van der Klift H, Franken P, Wijnen J, Breukel C, Bezrookove V, et al. A 10Mb paracentric inversion of chromosome arm 2p inactivates MSH2 and is responsible for HNPCC in a North-American kindred. Genes Chromosomes Cancer. 2002;35:49–57
  312. Wang Q, Lasset C, Desseigne F, Frappaz D, Bergeron C, Navarro C, et al. Neurofibromatosis and early onset of cancers in hMLH1-deficient children. Cancer Res. 1999;59:294–297
  313. Watson P, Lin K, Rodriguez-Bigas MA, Smyrk T, Lemon S, Shashidharan M, et al. Colorectal carcinoma survival among hereditary nonpolyposis colorectal cancer family members. Cancer. 1998;83:259–266
  314. Watson P, Lynch HT. Cancer risk in mismatch repair gene mutation carriers. Fam. Cancer. 2001;1:57–60
  315. Watson P, Vasen HFA, Mecklin J-P, Bernstein I, Aarnio M, Järvinen HJ, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int. J. Cancer. 2008;123:444–449
  316. Whitmore SE. BRCA1 mutations and survival in women with ovarian cancer. N. Engl. J. Med. 1997;336:1254–1255(letter)
  317. Whiteside D, McLeod R, Graham G, Steckley JL, Booth K, Somerville MJ, et al. A homozygous germ-line mutation in the human MSH2 gene predisposes to hematological malignancy and multiple café-au-lait spots. Cancer Res. 2002;62:359–362
  318. Wijnen J, de Leeuw W, Vasen H, van der Klift H, Møller P, Stormorken A, et al. Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat. Genet. 1999;23:142–144
  319. Wijnen J, van der Klift H, Vasen H, Khan PM, Menko F, Tops C, et al. MSH2 genomic deletions are a frequent cause of HNPCC. Nat. Genet. 1998;20:326–328
  320. Wijnen JT, Brohet RM, van Eijk R, Jagmohan-Changur S, Middeldorp A, Tops CM, et al. Chromosome 8q23.3 and 11q23.1 variants modify colorectal cancer risk in Lynch syndrome. Gastroenterology. 2009;136:131–137
  321. Woodruff JD. The pathogenesis of ovarian neoplasia. Johns Hopkins Med. J. 1979;144:117–120
  322. Woodward ER, Sleightholme HV, Considine AM, Williamson S, McHugo JM, Cruger DG. Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective. BJOG. 2007;114:1500–1509
  323. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378:789–792
  324. Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science. 1994;265:2088–2090
  325. Wright K, Wilson P, Morland S, Campbell I, Walsh M, Hurst T, et al. Beta-catenin mutation and expression analysis in ovarian cancer: exon 3 mutations and nuclear translocation in 16% of endometrioid tumours. Int. J. Cancer. 1999;82:625–629
  326. Wu R, Zhai Y, Fearon ER, Cho KR. Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res. 2001;61:8247–8255
  327. Wu Y, Berends MJW, Mensink RGJ, Kempinga C, Sijmons RH, van der Zee AGJ, et al. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. Am. J. Hum. Genet. 1999;65:1291–1298
  328. Yuan ZQ, Wong N, Foulkes WD, Alpert L, Manganaro F, Andreutti-Zaaugg C, et al. A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish HNPCC kindred: implications for clinical screening. J. Med. Genet. 1999;36:790–793
  329. Zhai QJ, Rosen DG, Lu K, Liu J. Loss of DNA mismatch repair protein hMSH6 in ovarian cancer is histotype-specific. Int. J. Clin. Exp. Pathol. 2008;1:502–509
  330. Ziogas A, Gildea M, Cohen P, Bringman D, Taylor TH, Seminara D, et al. Cancer risk estimates for family members of a population-based family registry for breast and ovarian cancer. Cancer Epidemiol. Biomarkers Prev. 2000;9:103–111
  331. Zweemer RP, van Diest PJ, Verheijen RH, Ryan A, Gille JJ, Sijmons RH, et al. Molecular evidence linking primary cancer of the fallopian tube to BRCA1 mutations. Gynecol. Oncol. 2000;76:45–50
  332. Zweemer RP, Verheijen RH, Coebergh JW, Jacobs IJ, van Diest PJ, Gille JJ, et al. Survival analysis in familial ovarian cancer, a case control study. Eur. J. Obstet. Gynecol. Reprod. Biol. 2001;98:219–223

PII: S1574-7891(09)00029-5

doi: 10.1016/j.molonc.2009.02.004

Molecular Oncology
Volume 3, Issue 2 , Pages 97-137 , April 2009