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Ovarian cancer in endometriosis: epidemiology, natural history, and clinical diagnosis

Abstract

We review whether endometriosis-associated ovarian cancer is a specific entity compared with ovarian cancer not associated with endometriosis, with respect to epidemiology, natural history, and clinical diagnosis; we present a review of the English-language literature for ovarian cancer in endometriosis with respect to these three features. A recent prospective study in Japan directly showed that, during a follow-up of up to 17 years of an ovarian endometrioma cohort (n = 6398), 46 incident ovarian cancers were identified, showing that the ovarian cancer risk was significantly elevated in patients with ovarian endometrioma (standardized incidence ratio [SIR], 8.95; 95% confidence interval [CI], 4.12 to 15.3). Advancing age (>40 years) and the size of the endometriomas (>9 cm) were independent predictors of the development of ovarian cancer among the women with ovarian endometrioma. Although some endometriosis lesions may predispose to clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) of the ovary, both of these cancers differ from the other histological types with respect to their clinical characteristics and carcinogenesis. In patients with endometriosis-associated ovarian cancer, benign-appearing ovarian masses are typically present several years before the diagnosis of the cancer. A slightly elevated carbohydrate antigen [CA] 125 level is also typically present many years before the diagnosis in these patients. However, serous-type ovarian cancer may exhibit a rapid progression possibly through de-novo carcinogenesis. Ovarian endometrioma could be viewed as a neoplastic process, particularly in perimenopausal women. Understanding the mechanisms of the development of endometriosis and elucidating its pathogenesis and pathophysiology are intrinsic to the prevention of endometriosis-associated ovarian cancer and the search for effective therapies.

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References

  1. Menon U, Talaat A, Jeyarajah AR, et al. (1999) Ultrasound assessment of ovarian cancer risk in postmenopausal women with CA125 elevation. Br J Cancer 80:1644–1647

    Article  CAS  PubMed  Google Scholar 

  2. Menon U, Jacobs IJ (2000) Recent developments in ovarian cancer screening. Curr Opin Obstet Gynecol 12:39–42

    Article  CAS  PubMed  Google Scholar 

  3. Schwartz PE (2001) Nongenetic screening of ovarian malignancies. Obstet Gynecol Clin North Am 28:637–651

    Article  CAS  PubMed  Google Scholar 

  4. Anderiesz C, Quinn MA (2003) Screening for ovarian cancer. Med J Aust 178:655–656

    PubMed  Google Scholar 

  5. Modugno F (2003) Ovarian Cancer and High-Risk Women Symposium Presenters. Ovarian cancer and high-risk women — implications for prevention, screening, and early detection. Gynecol Oncol 91:15–31

    Article  PubMed  Google Scholar 

  6. O’Rourke J, Mahon SM (2003) A comprehensive look at the early detection of ovarian cancer. Clin J Oncol Nurs 7:41–47

    Article  PubMed  Google Scholar 

  7. Jacobs I, Davies AP, Bridges J, et al. (1993) Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography. BMJ 306:1030–1034

    Article  CAS  PubMed  Google Scholar 

  8. van Nagell JR Jr, Gallion HH, Pavlik EJ, et al. (1995) Ovarian cancer screening. Cancer 76:2086–2091

    Article  PubMed  Google Scholar 

  9. Adonakis GL, Paraskevaidis E, Tsiga S, et al. (1996) A combined approach for the early detection of ovarian cancer in asymptomatic women. Eur J Obstet Gynecol Reprod Biol 65:221–225

    Article  CAS  PubMed  Google Scholar 

  10. MacDonald ND, Rosenthal AN, Jacobs IJ (1998) Screening for ovarian cancer. Ann Acad Med Singapore 27:676–682

    CAS  PubMed  Google Scholar 

  11. Jacobs IJ, Skates S, Davies AP, et al. (1996) Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study. BMJ 313:1355–1358

    CAS  PubMed  Google Scholar 

  12. Einhorn N, Bast R, Knapp R, et al. (2000) Long-term follow-up of the Stockholm screening study on ovarian cancer. Gynecol Oncol 79:466–470

    Article  CAS  PubMed  Google Scholar 

  13. Rosenthal A, Jacobs I (1998) Ovarian cancer screening. Semin Oncol 25:315–325

    CAS  PubMed  Google Scholar 

  14. Jacobs I, Stabile I, Bridges J, et al. (1988) Multimodal approach to screening for ovarian cancer. Lancet I:268–271

    Article  Google Scholar 

  15. Kobayashi H, Yamada Y, Sado T, et al. (2008) A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer 18:414–420

    Article  CAS  PubMed  Google Scholar 

  16. Menon U, Gentry-Maharaj A, Hallett R, et al. (2009) Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 10:327–340

    Article  PubMed  Google Scholar 

  17. Jacobs IJ, Skates SJ, MacDonald N, et al. (1999) Screening for ovarian cancer: a pilot randomised controlled trial. Lancet 353: 1207–1210

    Article  CAS  PubMed  Google Scholar 

  18. Daly M, Obrams GI (1998) Epidemiology and risk assessment for ovarian cancer. Semin Oncol 25:255–264

    CAS  PubMed  Google Scholar 

  19. Saito M, Aoki D, Susumu N, et al. (2005) Efficient screening for ovarian cancers using a combination of tumor markers CA602 and CA546. Int J Gynecol Cancer 15:37–44

    Article  CAS  PubMed  Google Scholar 

  20. Olive DL (2003) Medical therapy of endometriosis. Semin Reprod Med 21:209–222

    Article  CAS  PubMed  Google Scholar 

  21. Brinton LA, Gridley G, Persson I, et al. (1997) Cancer risk after a hospital discharge diagnosis of endometriosis. Am J Obstet Gynecol 176:572–579

    Article  CAS  PubMed  Google Scholar 

  22. Ness RB, Cramer DW, Goodman MT, et al. (2002) Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol 155:217–224

    Article  PubMed  Google Scholar 

  23. Brinton LA, Lamb EJ, Moghissi KS, et al. (2004) Ovarian cancer risk associated with varying causes of infertility. Fertil Steril 82:405–414

    Article  PubMed  Google Scholar 

  24. Borgfeldt C, Andolf E (2004) Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis. Acta Obstet Gynecol Scand 83:395–400

    Article  PubMed  Google Scholar 

  25. Kobayashi H, Sumimoto K, Moniwa N, et al. (2007) Risk of developing ovarian cancer among women with ovarian endometrioma: a cohort study in Shizuoka, Japan. Int J Gynecol Cancer 17: 37–43

    Article  CAS  PubMed  Google Scholar 

  26. Kawaguchi R, Tsuji Y, Haruta S, et al. (2008) Clinicopathologic features of ovarian cancer in patients with ovarian endometrioma. J Obstet Gynaecol Res 34:872–877

    Article  PubMed  Google Scholar 

  27. Kobayashi H, Sumimoto K, Kitanaka T, et al. (2008) Ovarian endometrioma — risks factors of ovarian cancer development. Eur J Obstet Gynecol Reprod Biol 138:187–193

    Article  PubMed  Google Scholar 

  28. Jimbo H, Yoshikawa H, Onda T, et al. (1997) Prevalence of ovarian endometriosis in epithelial ovarian cancer. Int J Gynaecol Obstet 59:245–250

    Article  CAS  PubMed  Google Scholar 

  29. Komiyama S, Aoki D, Tominaga E, et al. (1999) Prognosis of Japanese patients with ovarian clear cell carcinoma associated with pelvic endometriosis: clinicopathologic evaluation. Gynecol Oncol 72:342–346

    Article  CAS  PubMed  Google Scholar 

  30. Yoshikawa H, Jimbo H, Okada S, et al. (2000) Prevalence of endometriosis in ovarian cancer. Gynecol Obstet Invest 50(Suppl 1):11–17

    Article  PubMed  Google Scholar 

  31. Nishida M, Watanabe K, Sato N, et al. (2000) Malignant transformation of ovarian endometriosis. Gynecol Obstet Invest 50(Suppl 1):18–25

    Article  PubMed  Google Scholar 

  32. Okugawa K, Hirakawa T, Fukushima K, et al. (2001) Relationship between age, histological type, and size of ovarian tumors. Int J Gynaecol Obstet 74:45–50

    Article  CAS  PubMed  Google Scholar 

  33. Ness RB (2003) Endometriosis and ovarian cancer: thoughts on shared pathophysiology. Am J Obstet Gynecol 189:280–294

    Article  PubMed  Google Scholar 

  34. Purdie DM, Bain CJ, Siskind V, et al. (1999) Hormone replacement therapy and risk of epithelial ovarian cancer. Br J Cancer 81:559–563

    Article  CAS  PubMed  Google Scholar 

  35. Olson JE, Cerhan JR, Janney CA, et al. (2002) Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women’s Health Study. Cancer 94:1612–1618

    Article  PubMed  Google Scholar 

  36. Kobayashi H, Ooi H, Yamada Y, et al. (2007) Serum CA125 level before the development of ovarian cancer. Int J Gynaecol Obstet 99:95–99

    Article  CAS  PubMed  Google Scholar 

  37. Horiuchi A, Itoh K, Shimizu M, et al. (2003) Toward understanding the natural history of ovarian carcinoma development: a clinicopathological approach. Gynecol Oncol 88:309–317

    Article  PubMed  Google Scholar 

  38. Kurman RJ, Shih IeM (2008) Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol 27:151–160

    PubMed  Google Scholar 

  39. Yamaguchi K, Mandai M, Toyokuni S, et al. (2008) Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res 14:32–40

    Article  CAS  PubMed  Google Scholar 

  40. Kobayashi H, Kajiwara H, Kanayama S, et al. (2009) Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review). Oncol Rep 22:233–240

    Article  CAS  PubMed  Google Scholar 

  41. Leiserowitz GS, Gumbs JL, Oi R, et al. (2003) Endometriosis-related malignancies. Int J Gynecol Cancer 13:466–471

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Hiroshi Kobayashi.

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Kobayashi, H. Ovarian cancer in endometriosis: epidemiology, natural history, and clinical diagnosis. Int J Clin Oncol 14, 378 (2009). https://doi.org/10.1007/s10147-009-0931-2

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  • DOI: https://doi.org/10.1007/s10147-009-0931-2

Key words

  • Endometriosis
  • Ovarian cancer
  • Epidemiology
  • Diagnosis