Endometriosis and Cancer: Prevention and Diagnosis

In: ISGE Series · 2020 · pp. 133–147 · doi:10.1007/978-3-030-57866-4_13 · W3113330275
book-chapter OA: closed CC0 ⤵ 1 in-corpus citation
Full text JSON View on OpenAlex View at publisher
AI-generated summary by claude@2026-06+body, 2026-06-13

Endometriosis, a benign condition characterized by ectopic endometrial cells, shares features with cancer and may represent an initial stage, particularly in the ovary, though the link and premalignant status are debated.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text

This paper reviews evidence and gaps linking endometriosis to cancer, focusing on prevention and diagnosis, with particular attention to endometriosis-associated ovarian cancer (EAOC) and its heterogeneous histologic types. It summarizes shared cancer-like properties (evasion of apoptosis, proliferation and migration, implantation, neovascularization, immune-evasive microenvironment) and reports suggested genetic links involving driver mutations such as PIK3CA, KRAS, and ARID1A, while noting that the molecular mechanisms are not fully understood. For clinical translation, it emphasizes that results on the endometriosis–cancer association are controversial and that there are no conclusive data showing that specific screening protocols or prophylactic removal of endometriosis lesions reduce EAOC risk. This paper is centrally about endometriosis—specifically the reviewed relationship between endometriosis and ovarian cancer and implications for prevention and diagnosis.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Full text 15,680 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

Endometriosis is a benign reproductive tract disease, characterized by ectopic implantation of endometrial cells with elevated proliferation and migration capacity outside the uterus, mainly in the pelvis. Despite its benign nature, a number of studies support the notion that endometriosis may represent the initial stage of a neoplastic process, especially in the ovary. In fact, endometriosis shares several common features with cancer, including the ability to evade apoptosis, cell migration and proliferation, implantation at distant sites, neovascularization, creating a microenvironment eluding the immune system. A possible genetic link has been suggested in recent studies, highlighting driver mutations in PIK3CA, KRAS, ARID1A, and other genes. However, the underlying molecular and cellular mechanisms are still not fully understood. Endometriosis-associated ovarian cancer (EAOC) represents a heterogeneous group of different types of cancer including clear cell carcinoma, endometrioid carcinoma, and seromucinous borderline tumor, arising from coexistent endometriosis. However, clinical studies show controversial results on the link between endometriosis and cancer. Furthermore, considering the discrepancy between the low prevalence of EAOC and the high frequency of endometriosis, the hypothesis that endometriosis represents an exclusive premalignant condition is yet to be fully demonstrated. Atypical phenotypes of ovarian endometriosis require an appropriate imaging evaluation, but there are no conclusive data indicating that a specific screening protocol or the prophylactic removal of endometriosis lesions reduces the risk of EAOC. Further studies are needed to adequately explore clinical and basic science data on the link between endometriosis and cancer. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

References

Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382:1244–56. Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, Kohlmeier A, Yin P, Milad M, Wei J. Endometriosis. Endocr Rev. 2019b;40:1048–79. Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Primers. 2018 Jul 19;4(1):9. Wei JJ, William J, Bulun S. Endometriosis and ovarian cancer: a review of clinical, pathologic, and molecular aspects. Int J Gynecol Pathol. 2011;30:553–68. Ruderman R, Pavone ME. Ovarian cancer in endometriosis: an update on the clinical and molecular aspects. Minerva Ginecol. 2017;69:286–94. Mok SC, Kwong J, Welch WR, Samimi G, Ozbun L, Bonome T, Birrer MJ, Berkowitz RS, Wong KK. Etiology and pathogenesis of epithelial ovarian cancer. Dis Markers. 2007;23:367–76. Sampson JA. Endometrial carcinoma of the ovary arising in endometrial tissue in that organ. Arch Surg. 1925;10:1–72. Scott RB. Malignant changes in endometriosis. Obstet Gynecol. 1953;2:283–9. Grandi G, Toss A, Cortesi L, Botticelli L, Volpe A, Cagnacci A. The association between Endometriomas and ovarian Cancer: preventive effect of inhibiting ovulation and menstruation during reproductive life. Biomed Res Int. 2015;2015:751571. Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, et al. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol. 2012;13:385–94. Vercellini P, Parazzini F, Bolis G, Carinelli S, Dindelli M, Vendola N, Luchini L, Crosignani PG. Endometriosis and ovarian cancer. Am J Obstet Gynecol. 1993;169:181–2. Jimbo H, Yoshikawa H, Onda T, Yasugi T, Sakamoto A, Taketani Y. Prevalence of ovarian endometriosis in epithelial ovarian cancer. Int J Gynaecol Obstet. 1997;59:245–50. Dawson A, Fernandez ML, Anglesio M, Yong PJ, Carey MS. Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development. Ecancermedicalscience. 2018;12:803. Vercellini P, Viganò P, Buggio L, Makieva S, Scarfone G, Cribiù FM, Parazzini F, Somigliana E. Perimenopausal management of ovarian endometriosis and associated cancer risk: when is medical or surgical treatment indicated? Best Pract Res Clin Obstet Gynaecol. 2018;51:151–68. Heidemann LN, Hartwell D, Heidemann CH, Jochumsen KM. The relation between endometriosis and ovarian cancer - a review. Acta Obstet Gynecol Scand. 2014;93:20e31. Saavalainen L, Lassus H, But A, Tiitinen A, Härkki P, Gissler M, Pukkala E, Heikinheimo O. Risk of gynecologic Cancer according to the type of endometriosis. Obstet Gynecol. 2018;131:1095–102. Worley MJ, Welch WR, Berkowitz RS, Ng SW. Endometriosis-associated ovarian cancer: a review of pathogenesis. Int J Mol Sci. 2013;14:5367–79. Kobayashi H, Sumimoto K, Kitanaka T, Yamada Y, Sado T, Sakata M, Yoshida S, Kawaguchi R, Kanayama S, Shigetomi H, Haruta S, Tsuji Y, Ueda S. Terao T ovarian endometrioma--risks factors of ovarian cancer development. Eur J Obstet Gynecol Reprod Biol. 2008;138:187–93. Wang KC, Chang WH, Lee WL, Huang N, Huang HY, Yen MS, Guo CY, Wang PH. An increased risk of epithelial ovarian cancer in Taiwanese women with a new surgico-pathological diagnosis of endometriosis. BMC Cancer. 2014;14:831. Modugno F, Ness RB, Allen GO, Schildkraut JM, Davis FG, Goodman MT. Oral 920 contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with 921 and without endometriosis. Am J Obstet Gynecol. 2004;191:733–40. Stewart LM, Holman CD, Aboagye-Sarfo P, Finn JC, Preen DB. Hart R in vitro fertilization, endometriosis, nulliparity and ovarian cancer risk. Gynecol Oncol. 2013;128:260–4. Torng PL. Clinical implication for endometriosis associated with ovarian cancer. Gynecol Minim Invasive Ther. 2017;6:152–6. LaGrenade A, Silverberg SG. Ovarian tumors associated with atypical endometriosis. Case Reports Hum Pathol. 1988;19:1080–4. Herreros-Villanueva M, Chen CC, Tsai EM, Er TK. Endometriosis-associated ovarian cancer: what have we learned so far? Clin Chim Acta. 2019;493:63–72. Reis FM, Petraglia F, Taylor RN. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update. 2013 Jul-Aug;19(4):406–18. Anglesio MS, Papadopoulos N, Ayhan A, Nazeran TM, Noë M, Horlings HM, Lum A, Jones S, Senz J, Seckin T, Ho J, Wu RC, Lac V, Ogawa H, Tessier-Cloutier B, Alhassan R, Wang A, Wang Y, Cohen JD, Wong F, Hasanovic A, Orr N, Zhang M, Popoli M, McMahon W, Wood LD, Mattox A, Allaire C, Segars J, Williams C, Tomasetti C, Boyd N, Kinzler KW, Gilks CB, Diaz L, Wang TL, Vogelstein B, Yong PJ, Huntsman DG, Shih IM. Cancer-associated mutations in endometriosis without Cancer. N Engl J Med. 2017;376:1835–48. Bulun SE, Wan Y, Matei D. Epithelial mutations in endometriosis: link to ovarian Cancer. Endocrinology. 2019a;160:626–38. Ayhan A, Mao TL, Seckin T, Wu CH, Guan B, Ogawa H, et al. Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma. Int J Gynecol Cancer. 2012;22:1310–5. Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O. Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations. Mod Pathol. 2012;25:615–24. Yamamoto S, Tsuda H, Takano M, Iwaya K, Tamai S, Matsubara O. PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma. J Pathol. 2011;225:189–94. Smith IN, Briggs JM. Structural mutation analysis of PTEN and its genotype-phenotype correlations in endometriosis and Cancer. Proteins. 2016;84:1625–43. Govatati S, Kodati VL, Deenadayal M, Chakravarty B, Shivaji S, Bhanoori M. Mutations in the PTEN tumor gene and risk of endometriosis: a case-control study. Hum Reprod. 2014;29:324–36. Stewart CJ, Leung Y, Walsh MD, Walters RJ, Young JP, Buchanan DD. KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis. Hum Pathol. 2012;43:1177–83. Ren F, Wang D, Jiang Y, Ren F. Epigenetic inactivation of hMLH1 in the malignant transformation of ovarian endometriosis. Arch Gynecol Obstet. 2012;285:215–21. Hou Z, Sun L, Gao L, Liao L, Mao Y, Liu J. Cytokine array analysis of peritoneal fluid between women with endometriosis of different stages and those without endometriosis. Biomarkers. 2009;14:604–18. Darai E, Detchev R, Hugol D, Quang NT. Serum and cyst fluid levels of interleukin (IL)-6, IL-8 and tumour necrosis factor-alpha in women with endometriomas and benign and malignant cystic ovarian tumours. Hum Reprod. 2003;18:1681–5. Yilmaz BD, Bulun SE. Endometriosis and nuclear receptors. Hum Reprod Update. 2019;25:473–85. Monsivais D, Dyson MT, Yin P, Coon JS, Navarro A, Feng G, Malpani SS, Ono M, Ercan CM, Wei JJ, Pavone ME, Su E, Bulun SE. ERβ- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis. Mol Endocrinol. 2014;28:1304–15. Scutiero G, Iannone P, Bernardi G, Bonaccorsi G, Spadaro S, Volta CA, Greco P, Nappi L. Oxidative stress and endometriosis: a systematic review of the literature. Oxidative Med Cell Longev. 2017;2017:7265238. Kajiyama H, Suzuki S, Yoshihara M, Tamauchi S, Yoshikawa N, Niimi K, Shibata K, Kikkawa F. Endometriosis and cancer. Free Radic Biol Med. 2019;133:186–92. Laschke MW, Giebels C, Menger MD. Vasculogenesis: a new piece of the endometriosis puzzle. Hum Reprod Update. 2011;17:628–36. Králíčková M, Losan P, Vetvicka V. Endometriosis and cancer. Womens Health (Lond). 2014;10:591–7. Laschke MW, Menger MD. Basic mechanisms of vascularization in endometriosis and their clinical implications. Hum Reprod Update. 2018;24:207–24. Riccio LDGC, Santulli P, Marcellin L, Abrão MS, Batteux F, Chapron C. Immunology of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2018;50:39–49. Suryawanshi S, Huang X, Elishaev E, Budiu RA, Zhang L, Kim S, Donnellan N, Mantia-Smaldone G, Ma T, Tseng G, Lee T, Mansuria S, Edwards RP, Vlad AM. Complement pathway is frequently altered in endometriosis and endometriosis-associated ovarian cancer. Clin Cancer Res. 2014;20:6163–74. Exacoustos C, Manganaro L, Zupi E. Imaging for the evaluation of endometriosis and adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2014;28:655e81. Guerriero S, Ajossa S, Mais V, et al. The diagnosis of endometriomas using colour Doppler energy imaging. Hum Reprod. 1998;6:1691–5. Van Holsbeke C, Van Calster B, Guerriero S, Savelli L, Paladini D, Lissoni AA, Czekierdowski A, Fischerova D, Zhang J, Mestdagh G, Testa AC, Bourne T, Valentin L, Timmerman D. Endometriomas: their ultrasound characteristics. Ultrasound Obstet Gynecol. 2010;35:730–40. Guerriero S, Condous G, van den Bosch T, Valentin L, Leone FP, Van Schoubroeck D, Exacoustos C, Installé AJ, Martins WP, Abrao MS, Hudelist G, Bazot M, Alcazar JL, Gonçalves MO, Pascual MA, Ajossa S, Savelli L, Dunham R, Reid S, Menakaya U, Bourne T, Ferrero S, Leon M, Bignardi T, Holland T, Jurkovic D, Benacerraf B, Osuga Y, Somigliana E, Timmerman D. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group. Ultrasound Obstet Gynecol. 2016a;48:318–32. Guerriero S, Van Calster B, Somigliana E, Ajossa S, Froyman W, De Cock B, Coosemans A, Fischerová D, Van Holsbeke C, Alcazar JL, Testa AC, Valentin L, Bourne T, Timmerman D. Age-related differences in the sonographic characteristics of endometriomas. Hum Reprod. 2016b;31:1723–31. Testa AC, Timmerman D, Van Holsbeke C, Zannoni GF, Fransis S, Moerman P, Vellone V, Mascilini F, Licameli A, Ludovisi M, Di Legge A, Scambia G, Ferrandina G. Ovarian cancer arising in endometrioid cysts: ultrasound findings. Ultrasound Obstet Gynecol. 2011;38:99–106. Nezhat FR, Apostol R, Nezhat C, Pejovic T. New insights in the pathophysiology of ovarian cancer and implications for screening and prevention. Am J Obstet Gynecol. 2015;213:262–7. Tanase Y, Kawaguchi R, Takahama J, Kobayashi H. Factors that differentiate between endometriosis-associated ovarian Cancer and benign ovarian endometriosis with mural nodules. Magn Reson Med Sci. 2018;17:231–7. He ZX, Shi HH, Fan QB, Zhu L, Leng JH, Sun DW, et al. Predictive factors of ovarian carcinoma for women with ovarian endometrioma aged 45 years and older in China. J Ovarian Res. 2017;10:45. Kuo HH, Huang CY, Ueng SH, Huang KG, Lee CL, Yen CF. Unexpected epithelial ovarian cancers arising from presumed endometrioma: a 10-year retrospective analysis. Taiwan J Obstet Gynecol. 2017;56:55–61. Moro F, Magoga G, Pasciuto T, Mascilini F, Moruzzi MC, Fischerova D, Savelli L, Giunchi S, Mancari R, Franchi D, Czekierdowski A, Froyman W, Verri D, Epstein E, Chiappa V, Guerriero S, Zannoni GF, Timmerman D, Scambia G, Valentin L, Testa AC. Imaging in gynecological disease (13): clinical and ultrasound characteristics of endometrioid ovarian cancer. Ultrasound Obstet Gynecol. 2018;52:535–43. Dochez V, Caillon H, Vaucel E, Dimet J, Winer N, Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res. 2019;12:28. Moga MA, Bălan A, Dimienescu OG, Burtea V, Dragomir RM, Anastasiu CV. Circulating miRNAs as biomarkers for endometriosis and endometriosis-related ovarian Cancer-an overview. J Clin Med. 2019;8:735. Suryawanshi S, Vlad AM, Lin HM, Mantia-Smaldone G, Laskey R, Lee M, Lin Y, Donnellan N, Klein-Patel M, Lee T, Mansuria S, Elishaev E, Budiu R, Edwards RP, Huang X. Plasma microRNAs as novel biomarkers for endometriosis and endometriosis-associated ovarian cancer. Clin Cancer Res. 2013;19:1213–24. Taniguchi F. New knowledge and insights about the malignant transformation of endometriosis. J Obstet Gynaecol Res. 2017;43:1093. Rossing MA, Cushing-Haugen KL, Wicklund KG, Doherty JA, Weiss NS. Risk of epithelial ovarian cancer in relation to benign ovarian conditions and ovarian surgery. Cancer Causes Control. 2008;19:1357e64. Melin AS, Lundholm C, Malki N, Swahn ML, Sparèn P, Bergqvist A. Hormonal and surgical treatments for endometriosis and risk of epithelial ovarian cancer. Acta Obstet Gynecol Scand. 2013;92:546e54. National Institute for Health and Care Excellence. Endometriosis: diagnosis and management. NICE guideline NG73. September 2017. https://www.nice.org.uk/guidance/ng73/evidence/full-guideline-pdf-4550371315. Wilbur MA, Shih IM, Segars JH, Fader AN. Cancer implications for patients with endometriosis. Semin Reprod Med. 2017;35:110–6. Paik ES, Kim TJ, Choi CH, Kim BG, Bae DS, Lee JW. Clinical outcomes of patients with clear cell and endometrioid ovarian cancer arising from endometriosis. J Gynecol Oncol. 2018;29:e18. Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2021 International Society of Gynecological Endocrinology About this chapter Cite this chapter Vannuccini, S., Clemenza, S., Petraglia, F. (2021). Endometriosis and Cancer: Prevention and Diagnosis. In: Genazzani, A.R., Nisolle, M., Petraglia, F., Taylor, R.N. (eds) Endometriosis Pathogenesis, Clinical Impact and Management. ISGE Series. Springer, Cham. https://doi.org/10.1007/978-3-030-57866-4_13 Download citation DOI: https://doi.org/10.1007/978-3-030-57866-4_13 Published: Publisher Name: Springer, Cham Print ISBN: 978-3-030-57865-7 Online ISBN: 978-3-030-57866-4 eBook Packages: MedicineMedicine (R0)

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (67)

Cited by (1)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
License: CC0 · commercial use OK