Skip to main content
SpringerLink
Log in

Pathology and Molecular Pathology of Uterine and Ovarian Cancers

  • Chapter
  • First Online:
Pathology and Epidemiology of Cancer

  • 2969 Accesses

Abstract

In this chapter, the embryology and development of the Müllerian tract is first introduced. The chapter is then divided into two major sections: pathology of the uterus and the ovary. In the uterine portion, benign endometrium is first discussed and the dating patterns for cyclic endometrium are described. Other benign, pre-malignant and cancer histology, genetics and genomics are then discussed. For the ovarian portion, in a similar fashion, normal ovarian histology is first introduced, followed by non-neoplastic and neoplastic conditions. The chapter is concluded with genetics and genomics of ovarian cancers. Endometrial carcinoma is the most common malignancy while ovarian carcinoma is one of the deadliest diseases of the Müllerian tract. Thus, understanding the genetic and molecular alterations underlying these cancers is essential in guiding and developing future novel therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Crosby WM, Hill EC. Embryology of the mullerian duct system. Obstet Gynecol. 1962;20:507–15.

    CAS  PubMed  Google Scholar 

  2. T.W.S. Langman’s Medical Embryology. 5 ed. London: Williams and Wilkins; 1985.

    Google Scholar 

  3. Josso N, Racine C, di Clemente N, Rey R, Xavier F. The role of anti-Mullerian hormone in gonadal development. Mol Cell Endocrinol. 1998;145:3–7.

    Article  PubMed  Google Scholar 

  4. Hunter RHF. Differentiation of the genital duct system. In: Hunter RHF, editor. Sex determination, differentiation, and intersexuality in placental mammals. Cambridge: Cambridge University Press; 1995. p. 107–38.

    Chapter  Google Scholar 

  5. Moore KL. Before we are born: basic enbryology and birth defects. Philadelphia: Saunders; 1974.

    Google Scholar 

  6. Brennan J, Capel B. One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet. 2004;5:509–21.

    Article  CAS  PubMed  Google Scholar 

  7. Mackay S. Gonadal development in mammals at the cellular and molecular level. Int Rev Cytol. 2000;200.

    Google Scholar 

  8. Hunter RHF. Differentiation of the gonads. In: Hunter RHF, editor. Sex determination, differentiation, and intersexuality in placental mammals. Cambridge: Cambridge University Press; 1995. p. 69–106.

    Chapter  Google Scholar 

  9. Nicosia SV. Morphological changes of the human ovary throughout life. In: Serra GB, editor. The ovary. New York: Raven Press; 1983. p. 57–81.

    Google Scholar 

  10. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1(1):3–25.

    Article  Google Scholar 

  11. Crum CP, Hornstein MD, Nucci MR, Mutter GL. Hertig and beyond: a systematic and practical approach to the endometrial biopsy. Advances in anatomic pathology. 2003;10(6):301–18.

    Article  PubMed  Google Scholar 

  12. Crum CP, Nucci MR, Lee KR. Diagnostic gynecologic and obstetric pathology. 2nd ed. Philadelphia, PA: Saunders/Elsevier; 2011. xiv, 1202 p. p.

    Google Scholar 

  13. Ferenczy A. Pathophysiology of endometrial bleeding. Maturitas. 2003;45(1):1–14.

    Article  CAS  PubMed  Google Scholar 

  14. Vakiani M, Vavilis D, Agorastos T, Stamatopoulos P, Assimaki A, Bontis J. Histopathological findings of the endometrium in patients with dysfunctional uterine bleeding. Clin Exp Obstet Gynecol. 1996;23(4):236–9.

    CAS  PubMed  Google Scholar 

  15. Parazzini F, La Vecchia C, Bocciolone L, Franceschi S. The epidemiology of endometrial cancer. Gynecol Oncol. 1991;41(1):1–16.

    Article  CAS  PubMed  Google Scholar 

  16. Montgomery BE, Daum GS, Dunton CJ. Endometrial hyperplasia: a review. Obstet Gynecol Surv. 2004;59(5):368–78.

    Article  PubMed  Google Scholar 

  17. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer. 1985;56(2):403–12.

    Article  CAS  PubMed  Google Scholar 

  18. Mutter GL, Zaino RJ, Baak JP, Bentley RC, Robboy SJ. Benign endometrial hyperplasia sequence and endometrial intraepithelial neoplasia. Int J Gynecol Pathol. 2007;26(2):103–14.

    Article  PubMed  Google Scholar 

  19. Baak JP, Mutter GL, Robboy S, van Diest PJ, Uyterlinde AM, Orbo A, et al. The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system. Cancer. 2005;103(11):2304–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mutter GL, Baak JP, Crum CP, Richart RM, Ferenczy A, Faquin WC. Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry. J Pathol. 2000;190(4):462–9.

    Article  CAS  PubMed  Google Scholar 

  21. Mutter GL, Kauderer J, Baak JP, Alberts D. Biopsy histomorphometry predicts uterine myoinvasion by endometrial carcinoma: a Gynecologic Oncology Group study. Hum Pathol. 2008;39(6):866–74.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Mutter GL. Histopathology of genetically defined endometrial precancers. Int J Gynecol Pathol. 2000;19(4):301–9.

    Article  CAS  PubMed  Google Scholar 

  23. National Cancer Institute. Surveillance epidemiology and end results 2014 (Internet). (cited 11 Feb 2015). Available from http://seer.cancer.gov/statfacts/html/ovary.html.

  24. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10–7.

    Article  CAS  PubMed  Google Scholar 

  25. Sherman ME. Theories of endometrial carcinogenesis: a multidisciplinary approach. Mod Pathol. 2000;13(3):295–308.

    Article  CAS  PubMed  Google Scholar 

  26. Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet Official Organ Int Fed Gynaecol Obstet. 2006;95 Suppl 1:S105–43.

    Google Scholar 

  27. Barrow E, Robinson L, Alduaij W, Shenton A, Clancy T, Lalloo F, et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clin Genet. 2009;75(2):141–9.

    Article  CAS  PubMed  Google Scholar 

  28. Bonadona V, Bonaiti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305(22):2304–10.

    Google Scholar 

  29. Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012;18(2):400–7.

    Google Scholar 

  30. Zaino RJ, Kurman RJ, Diana KL, Morrow CP. The utility of the revised International Federation of Gynecology and Obstetrics histologic grading of endometrial adenocarcinoma using a defined nuclear grading system. A Gynecologic Oncology Group study. Cancer. 1995;75(1):81–6.

    Article  CAS  PubMed  Google Scholar 

  31. Ross JC, Eifel PJ, Cox RS, Kempson RL, Hendrickson MR. Primary mucinous adenocarcinoma of the endometrium. A clinicopathologic and histochemical study. Am J Surg Pathol. 1983;7(8):715–29.

    Article  CAS  PubMed  Google Scholar 

  32. Kurman RJ. International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of female reproductive organs. 4th ed. Lyon: International Agency for Research on Cancer; 2014. 307 pp.

    Google Scholar 

  33. Evans MJ, Langlois NE, Kitchener HC, Miller ID. Is there an association between long-term tamoxifen treatment and the development of carcinosarcoma (malignant mixed Mullerian tumor) of the uterus? Int J Gynecol Cancer. 1995;5(4):310–3.

    Article  PubMed  Google Scholar 

  34. Hubalek M, Ramoni A, Mueller-Holzner E, Marth C. Malignant mixed mesodermal tumor after tamoxifen therapy for breast cancer. Gynecol Oncol. 2004;95(1):264–6.

    Article  PubMed  Google Scholar 

  35. Costa MJ, Guinee D Jr. CD34 immunohistochemistry in female genital tract carcinosarcoma (malignant mixed mullerian tumors) supports a dominant role of the carcinomatous component. Appl Immunohistochem Mol Morphol. 2000;8(4):293–9.

    CAS  PubMed  Google Scholar 

  36. Seidman JD, Chauhan S. Evaluation of the relationship between adenosarcoma and carcinosarcoma and a hypothesis of the histogenesis of uterine sarcomas. Int J Gynecol Pathol. 2003;22(1):75–82.

    Article  PubMed  Google Scholar 

  37. Sreenan JJ, Hart WR. Carcinosarcomas of the female genital tract. A pathologic study of 29 metastatic tumors: further evidence for the dominant role of the epithelial component and the conversion theory of histogenesis. Am J Surg Pathol. 1995;19(6):666–74.

    Article  CAS  PubMed  Google Scholar 

  38. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet Official Organ Int Fed Gynaecol Obstet. 2009;105(2):103–4.

    Article  Google Scholar 

  39. Lancaster JM, Powell CB, Chen LM, Richardson DL. Committee SGOCP. Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2015;136(1):3–7.

    Article  PubMed  Google Scholar 

  40. Bonadona V, Bonaiti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305(22):2304–10.

    Article  CAS  PubMed  Google Scholar 

  41. Engel C, Loeffler M, Steinke V, Rahner N, Holinski-Feder E, Dietmaier W, et al. Risks of less common cancers in proven mutation carriers with lynch syndrome. J Clin Oncol. 2012;30(35):4409–15.

    Article  PubMed  Google Scholar 

  42. Watson P, Vasen HF, Mecklin JP, Bernstein I, Aarnio M, Jarvinen HJ, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer. 2008;123(2):444–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ketabi Z, Bartuma K, Bernstein I, Malander S, Gronberg H, Bjorck E, et al. Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors. Gynecol Oncol. 2011;121(3):462–5.

    Article  PubMed  Google Scholar 

  44. Buchanan DD, Tan YY, Walsh MD, Clendenning M, Metcalf AM, Ferguson K, et al. Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing. J Clin Oncol. 2014;32(2):90–100.

    Article  CAS  PubMed  Google Scholar 

  45. Simpkins SB, Bocker T, Swisher EM, Mutch DG, Gersell DJ, Kovatich AJ, et al. MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers. Hum Mol Genet. 1999;8(4):661–6.

    Article  CAS  PubMed  Google Scholar 

  46. Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, Broderick P, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 2013;45(2):136–44.

    Article  CAS  PubMed  Google Scholar 

  47. Riegert-Johnson DL, Gleeson FC, Roberts M, Tholen K, Youngborg L, Bullock M, et al. Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients. Hered Cancer Clin Pract. 2010;8(1):6.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105(21):1607–16.

    Article  CAS  PubMed  Google Scholar 

  49. Pilarski R, Stephens JA, Noss R, Fisher JL, Prior TW. Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet. 2011;48(8):505–12.

    Article  CAS  PubMed  Google Scholar 

  50. Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012;18(2):400–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bubien V, Bonnet F, Brouste V, Hoppe S, Barouk-Simonet E, David A, et al. High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome. J Med Genet. 2013;50(4):255–63.

    Article  CAS  PubMed  Google Scholar 

  52. Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, et al. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet. 2011;88(1):42–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Church DN, Briggs SE, Palles C, Domingo E, Kearsey SJ, Grimes JM, et al. DNA polymerase epsilon and delta exonuclease domain mutations in endometrial cancer. Hum Mol Genet. 2013;22(14):2820–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Briggs S, Tomlinson I. Germline and somatic polymerase epsilon and delta mutations define a new class of hypermutated colorectal and endometrial cancers. J Pathol. 2013;230(2):148–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Valle L, Hernandez-Illan E, Bellido F, Aiza G, Castillejo A, Castillejo MI, et al. New insights into POLE and POLD1 germline mutations in familial colorectal cancer and polyposis. Hum Mol Genet. 2014;23(13):3506–12.

    Article  CAS  PubMed  Google Scholar 

  56. Carvajal-Carmona LG, O’Mara TA, Painter JN, Lose FA, Dennis J, Michailidou K, et al. Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk. Hum Genet. 2015;134(2):231–45.

    Article  CAS  PubMed  Google Scholar 

  57. Painter JN, O’Mara TA, Batra J, Cheng T, Lose FA, Dennis J, et al. Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk. Hum Mol Genet. 2015;24(5):1478–92.

    Article  CAS  PubMed  Google Scholar 

  58. Spurdle AB, Thompson DJ, Ahmed S, Ferguson K, Healey CS, O’Mara T, et al. Genome-wide association study identifies a common variant associated with risk of endometrial cancer. Nat Genet. 2011;43(5):451–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Dunlop MG, Tenesa A, Farrington SM, Ballereau S, Brewster DH, Koessler T, et al. Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals. Gut. 2013;62(6):871–81.

    Article  CAS  PubMed  Google Scholar 

  60. O’Hara AJ, Bell DW. The genomics and genetics of endometrial cancer. Adv Genomics Genet. 2012;2012(2):33–47.

    PubMed  PubMed Central  Google Scholar 

  61. Le Gallo M, Bell DW. The emerging genomic landscape of endometrial cancer. Clin Chem. 2014;60(1):98–110.

    Article  PubMed  Google Scholar 

  62. Cancer Genome Atlas Research N, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.

    Google Scholar 

  63. Satoh M. Histogenesis and organogenesis of the gonad in human embryos. J Anat. 1991;77:85–107.

    Google Scholar 

  64. Strickler RC, Kelly RW, Askin FB. Postmenopausal ovarian follicle cyst: an unusual cause of estrogen excess. Int J Gynecol Pathol. 1984;3:318–22.

    Article  CAS  PubMed  Google Scholar 

  65. Dunaif A, Thomas A. Current concepts in polycystic ovary syndrome. Annu Rev Med. 2001;52:401–19.

    Article  CAS  PubMed  Google Scholar 

  66. Hardiman P, Pillary OS, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet. 2003;361:1810–2.

    Article  PubMed  Google Scholar 

  67. Sasamo H, Fukunaga M, Rojas M, Silverberg SG. Hyperthecosis of the ovary: clinicopathologic study of 19 caseswith immunohistochemical analysis of steroidogenic enzymes. Int J Gynecol Pathol. 1989;8:311–20.

    Article  Google Scholar 

  68. Shih IM, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004;164(5):1511–8.

    Google Scholar 

  69. Kurman RJ, Shih IM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010;34(3):433–43.

    Article  PubMed  PubMed Central  Google Scholar 

  70. 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(2):161–9.

    Article  PubMed  Google Scholar 

  71. 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(2):230–6.

    Article  PubMed  Google Scholar 

  72. Della Pepa C, Tonini G, Santini D, Losito S, Pisano C, Di Napoli M, et al. Low grade serous ovarian carcinoma: from the molecular characterization to the best therapeutic strategy. Cancer Treat Rev. 2015;41(2):136–43.

    Google Scholar 

  73. Chao A, Chao A, Yen YS, Huang CH. Abdominal compartment syndrome secondary to ovarian mucinous cystadenoma. Obstet Gynecol. 2004;104(5 Pt 2):1180–2.

    Article  PubMed  Google Scholar 

  74. Bicer S, Erkul Z, Demiryilmaz I, Peker N. A 9-kg ovarian mucinous cystadenoma in a 14-year-old premenarchal girl. Am J Case Rep. 2014;15:326–9.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Lee KR, Scully RE. Mucinous tumors of the ovary: a clinicopathologic study of 196 borderline tumors (of intestinal type) and carcinomas, including an evaluation of 11 cases with ‘pseudomyxoma peritonei’. Am J Surg Pathol. 2000;24(11):1447–64.

    Article  CAS  PubMed  Google Scholar 

  76. Cuatrecasas M, Villanueva A, Matias-Guiu X, Prat J. K-ras mutations in mucinous ovarian tumors: a clinicopathologic and molecular study of 95 cases. Cancer. 1997;79(8):1581–6.

    Article  CAS  PubMed  Google Scholar 

  77. Garrett AP, Lee KR, Colitti CR, Muto MG, Berkowitz RS, Mok SC. K-ras mutation may be an early event in mucinous ovarian tumorigenesis. Int J Gynecol Pathol. 2001;20(3):244–51.

    Article  CAS  PubMed  Google Scholar 

  78. Falkenberry SS, Steinhoff MM, Gordinier M, Rappoport S, Gajewski W, Granai CO. Synchronous endometrioid tumors of the ovary and endometrium. A clinicopathologic study of 22 cases. J Reprod Med. 1996;41(10):713–8.

    CAS  PubMed  Google Scholar 

  79. Sheu BC, Lin HH, Chen CK, Chao KH, Shun CT, Huang SC. Synchronous primary carcinomas of the endometrium and ovary. Int J Gynaecol Obstet Official Organ Int Fed Gynaecol Obstet. 1995;51(2):141–6.

    Article  CAS  Google Scholar 

  80. Zaino RJ, Unger ER, Whitney C. Synchronous carcinomas of the uterine corpus and ovary. Gynecol Oncol. 1984;19(3):329–35.

    Article  CAS  PubMed  Google Scholar 

  81. Heitz F, Amant F, Fotopoulou C, Battista MJ, Wimberger P, Traut A, et al. Synchronous ovarian and endometrial cancer—an international multicenter case-control study. Int J Gynecol Cancer. 2014;24(1):54–60.

    Article  PubMed  Google Scholar 

  82. Liu Y, Li J, Jin H, Lu Y, Lu X. Clinicopathological characteristics of patients with synchronous primary endometrial and ovarian cancers: a review of 43 cases. Oncol Lett. 2013;5(1):267–70.

    PubMed  Google Scholar 

  83. Zaino R, Whitney C, Brady MF, DeGeest K, Burger RA, Buller RE. Simultaneously detected endometrial and ovarian carcinomas—a prospective clinicopathologic study of 74 cases: a gynecologic oncology group study. Gynecol Oncol. 2001;83(2):355–62.

    Article  CAS  PubMed  Google Scholar 

  84. Chan JK, Teoh D, Hu JM, Shin JY, Osann K, Kapp DS. Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecol Oncol. 2008;109(3):370–6.

    Article  PubMed  Google Scholar 

  85. Ogawa S, Kaku T, Amada S, Kobayashi H, Hirakawa T, Ariyoshi K, et al. Ovarian endometriosis associated with ovarian carcinoma: a clinicopathological and immunohistochemical study. Gynecol Oncol. 2000;77(2):298–304.

    Article  CAS  PubMed  Google Scholar 

  86. Kandalaft PL, Gown AM, Isacson C. The lung-restricted marker napsin A is highly expressed in clear cell carcinomas of the ovary. Am J Clin Pathol. 2014;142(6):830–6.

    Article  PubMed  Google Scholar 

  87. Takeuchi T, Ohishi Y, Imamura H, Aman M, Shida K, Kobayashi H, et al. Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma. Am J Surg Pathol. 2013;37(7):1091–9.

    Article  PubMed  Google Scholar 

  88. Prat J, Oncology FCoG. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet Official Organ Int Fed Gynaecol Obstet. 2014;124(1):1–5.

    Google Scholar 

  89. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  PubMed  Google Scholar 

  90. Weissman SM, Weiss SM, Newlin AC. Genetic testing by cancer site: ovary. Cancer J. 2012;18(4):320–7.

    Article  PubMed  Google Scholar 

  91. Stratton JF, Pharoah P, Smith SK, Easton D, Ponder BA. A systematic review and meta-analysis of family history and risk of ovarian cancer. Br J Obstet Gynaecol. 1998;105(5):493–9.

    Article  CAS  PubMed  Google Scholar 

  92. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Moyer VA, Force USPST. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(4):271–81.

    Google Scholar 

  94. Lu KH, Daniels M. Endometrial and ovarian cancer in women with Lynch syndrome: update in screening and prevention. Fam Cancer. 2013;12(2):273–7.

    Article  PubMed  Google Scholar 

  95. Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet. 2010;42(5):410–4.

    Article  CAS  PubMed  Google Scholar 

  96. Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet. 2011;43(9):879–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bolton KL, Tyrer J, Song H, Ramus SJ, Notaridou M, Jones C, et al. Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nat Genet. 2010;42(10):880–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Goode EL, Chenevix-Trench G, Song H, Ramus SJ, Notaridou M, Lawrenson K, et al. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet. 2010;42(10):874–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Song H, Ramus SJ, Tyrer J, Bolton KL, Gentry-Maharaj A, Wozniak E, et al. A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nat Genet. 2009;41(9):996–1000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Pharoah PD, Tsai YY, Ramus SJ, Phelan CM, Goode EL, Lawrenson K, et al. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nat Genet. 2013;45(4):362–70, 70e1–2.

    Google Scholar 

  101. Permuth-Wey J, Lawrenson K, Shen HC, Velkova A, Tyrer JP, Chen Z, et al. Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. Nat Commun. 2013;4:1627.

    Google Scholar 

  102. Bojesen SE, Pooley KA, Johnatty SE, Beesley J, Michailidou K, Tyrer JP, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. 2013;45(4):371–84, 84e1–2.

    Google Scholar 

  103. Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, et al. Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nat Genet. 2015;47(2):164–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Carvajal-Carmona LG. Challenges in the identification and use of rare disease-associated predisposition variants. Curr Opin Genet Dev. 2010; 20:277–281.

    Google Scholar 

  105. Chenevix-Trench G, Milne RL, Antoniou AC, Couch FJ, Easton DF, Goldgar DE, et al. An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). Breast Cancer Res. 2007;9(2):104.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Couch FJ, Gaudet MM, Antoniou AC, Ramus SJ, Kuchenbaecker KB, Soucy P, et al. Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev. 2012;21(4):645–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Couch FJ, Wang X, McGuffog L, Lee A, Olswold C, Kuchenbaecker KB, et al. Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk. PLoS Genet. 2013;9(3):e1003212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Ramus SJ, Kartsonaki C, Gayther SA, Pharoah PD, Sinilnikova OM, Beesley J, et al. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2011;103(2):105–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Ahmed AA, Etemadmoghadam D, Temple J, Lynch AG, Riad M, Sharma R, et al. Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol. 2010;221(1):49–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609–15.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medicine, University of California at Davis, 4400V. St., PATH Building, Sacramento, CA, 95817, USA

    Eric C. Huang

  2. School of Medicine, Boston University, 670 Albany St., Boston, MA, 02118, USA

    David W. Kindelberger

  3. Genome Center and School of Medicine, University of California at Davis, GBSF, 451 Health Science Dr., Davis, CA, 95616, USA

    Luis G. Carvajal-Carmona

Authors
  1. Eric C. Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David W. Kindelberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luis G. Carvajal-Carmona
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric C. Huang .

Editor information

Editors and Affiliations

  1. Center for Molecular Oncologic Pathology, Dana Farber Cancer Institute, Boston, Massachusetts, USA

    Massimo Loda

  2. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA

    Lorelei A. Mucci

  3. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA

    Megan L. Mittelstadt

  4. King’s College London, Guy’s Hospital, London, United Kingdom

    Mieke Van Hemelrijck

  5. Department of Pathology, Dana-Farber Cancer Institute and Brigham & Women’s Hospital, Boston, Massachusetts, USA

    Maura Bríd Cotter

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Huang, E.C., Kindelberger, D.W., Carvajal-Carmona, L.G. (2017). Pathology and Molecular Pathology of Uterine and Ovarian Cancers. In: Loda, M., Mucci, L., Mittelstadt, M., Van Hemelrijck, M., Cotter, M. (eds) Pathology and Epidemiology of Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-35153-7_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-35153-7_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-35151-3

  • Online ISBN: 978-3-319-35153-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation