Geburtshilfe Frauenheilkd 2016; 76(02): 176-181
DOI: 10.1055/s-0035-1558239
Review
GebFra Science
Georg Thieme Verlag KG Stuttgart · New York

Endometriosis-associated Malignancy

Endometriose-assoziierte Malignome
N. Krawczyk
1   Department of Obstetrics and Gynecology, University of Düsseldorf, Düsseldorf
,
M. Banys-Paluchowski
1   Department of Obstetrics and Gynecology, University of Düsseldorf, Düsseldorf
4   Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg
,
D. Schmidt
2   Synlab MVZ Pathologie Mannheim GmbH, A2, 2, Mannheim
,
U. Ulrich
3   Department of Obstetrics and Gynecology, Martin Luther Hospital, Berlin
,
T. Fehm
1   Department of Obstetrics and Gynecology, University of Düsseldorf, Düsseldorf
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 17. Juli 2015
revised 13. September 2015

accepted 18. Oktober 2015

Publikationsdatum:
29. Februar 2016 (online)

Abstract

Endometriosis is a common condition in women of reproductive age. According to several epidemiological studies endometriosis may be associated with increased risk of various malignancies. However, endometriosis-associated malignancy (EAM) is defined by certain histological criteria. About 80 % of EAM have been found in the ovary, whereas 20 % are localized in extragonadal sites like intestine, rectovaginal septum, abdominal wall, pleura and others. Some authors suggest that EAM arise from atypical endometriosis as an intermediate lesion between endometriosis and cancer. Moreover, a number of genetic alterations, like loss of heterozygosity (LOH), PTEN, ARID1 A and p53 mutations have been found in both endometriosis and EAM. Endometriosis-associated ovarian cancer (EAOC) is mostly a well or intermediately differentiated tumor of endometrioid or clear cell histological sub-type. Women affected by EAOC are on average five to ten years younger than non-EAOC patients; in most of the cases EAOC is a low stage disease with favorable clinical outcome. Since EAM is a rare condition systematic data on EAM are still missing. A systematic retrospective study on endometriosis-associated malignancies (EAM study) is currently being conducted by the Endometriosis Research Foundation together with the study groups on ovarian and uterine tumors of the working group for gynecological oncology (AGO) (gyn@mlk-berlin.de).

Zusammenfassung

Endometriose stellt eine häufige, gutartige Erkrankung der Frau im reproduktiven Alter dar. Epidemiologischen Studien zufolge gibt es eine Assoziation zwischen Endometriose und dem Risiko, an verschiedenen Malignomen zu erkranken. Die Diagnose von endometrioseassoziierten Malignomen (EAM) kann jedoch erst nach Erfüllen einiger histologischer Kriterien erfolgen. Circa 80 % der EAM entstehen im Ovar, während in 20 % der Fälle eine primär extragonadale Manifestation möglich ist (Darm, rektovaginales Septum, Bauchwand, Pleura u. a.). Eine der Entstehungstheorien besagt, dass EAM direkt aus der atypischen Endometriose entstehen. Darüber hinaus wurden bis dato zahlreiche Mutationen wie PTEN-, ARID1 A- oder p53-Mutationen sowie Heterozygotieverlust sowohl in der Endometriose als auch in EAM nachgewiesen. Ein endometrioseassoziiertes Ovarialkarzinom (EAOC) stellt meist ein gut oder mittelgradig differenziertes Karzinom vom endometroiden oder klarzelligen Typ dar. EAOC-Patientinnen sind durchschnittlich 5–10 Jahre jünger als Frauen mit Nicht-EAOC; in den meisten Fällen wird das EAOC im frühen Stadium diagnostiziert und hat eine günstige Prognose. Aufgrund des seltenen Auftretens der EAM liegen in der Literatur nur wenige systematische Studien zu dieser Entität vor. Eine retrospektive Studie zur Charakterisierung endometrioseassoziierter Malignome (EAM-Studie) wird aktuell von der Stiftung Endometrioseforschung gemeinsam mit den Kommissionen Ovar und Uterus der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) durchgeführt (gyn@mlk-berlin.de).

 
  • References

  • 1 Vignali M, Infantino M, Matrone R et al. Endometriosis: novel etiopathogenetic concepts and clinical perspectives. Fertil Steril 2002; 78: 665-678
  • 2 Sayasneh A, Tsivos D, Crawford R. Endometriosis and ovarian cancer: a systematic review. ISRN Obstet Gynecol 2011; 2011: 140310
  • 3 Berkley KJ, Rapkin AJ, Papka RE. The pains of endometriosis. Science 2005; 308: 1587-1589
  • 4 Gazvani R, Templeton A. New considerations for the pathogenesis of endometriosis. Int J Gynaecol Obstet 2002; 76: 117-126
  • 5 Siufi Neto J, Kho RM, Siufi DF et al. Cellular, histologic, and molecular changes associated with endometriosis and ovarian cancer. J Minim Invasive Gynecol 2014; 21: 55-63
  • 6 Ness RB. Endometriosis and ovarian cancer: thoughts on shared pathophysiology. Am J Obstet Gynecol 2003; 189: 280-294
  • 7 Vercellini P, Parazzini F, Bolis G et al. Endometriosis and ovarian cancer. Am J Obstet Gynecol 1993; 169: 181-182
  • 8 Brinton LA, Gridley G, Persson I et al. Cancer risk after a hospital discharge diagnosis of endometriosis. Am J Obstet Gynecol 1997; 176: 572-579
  • 9 Heidemann LN, Hartwell D, Heidemann CH et al. The relation between endometriosis and ovarian cancer – a review. Acta Obstet Gynecol Scand 2014; 93: 20-31
  • 10 Ness RB, Grisso JA, Cottreau C et al. Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer. Epidemiology 2000; 11: 111-117
  • 11 Ness RB, Cramer DW, Goodman MT et al. Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol 2002; 155: 217-224
  • 12 Olson JE, Cerhan JR, Janney CA et al. Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Womenʼs Health Study. Cancer 2002; 94: 1612-1618
  • 13 Brinton LA, Lamb EJ, Moghissi KS et al. Ovarian cancer risk associated with varying causes of infertility. Fertil Steril 2004; 82: 405-414
  • 14 Borgfeldt C, Andolf E. Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis. Acta Obstet Gynecol Scand 2004; 83: 395-400
  • 15 Modugno F, Ness RB, Allen GO et al. Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis. Am J Obstet Gynecol 2004; 191: 733-740
  • 16 Melin A, Sparen P, Persson I et al. Endometriosis and the risk of cancer with special emphasis on ovarian cancer. Hum Reprod 2006; 21: 1237-1242
  • 17 Melin A, Sparen P, Bergqvist A. The risk of cancer and the role of parity among women with endometriosis. Hum Reprod 2007; 22: 3021-3026
  • 18 Pearce CL, Templeman C, Rossing MA et al. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 2012; 13: 385-394
  • 19 Munksgaard PS, Blaakaer J. The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations. Gynecol Oncol 2012; 124: 164-169
  • 20 Kok VC, Tsai HJ, Su CF et al. The risks for ovarian, endometrial, breast, colorectal, and other cancers in women with newly diagnosed endometriosis or adenomyosis: a population-based study. Int J Gynecol Cancer 2015; 25: 968-976
  • 21 Ulrich U, Buchweitz O, Greb R et al. Interdisciplinary S2k guidelines for the diagnosis and treatment of endometriosis: short version – AWMF Registry No. 015-045, August 2013. Geburtsh Frauenheilk 2013; 73: 890-898
  • 22 Stewart LM, Holman CD, Aboagye-Sarfo P et al. In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk. Gynecol Oncol 2013; 128: 260-264
  • 23 Buis CC, van Leeuwen FE, Mooij TM et al. Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis. Hum Reprod 2013; 28: 3358-3369
  • 24 Kobayashi H, Sumimoto K, Moniwa N et al. Risk of developing ovarian cancer among women with ovarian endometrioma: a cohort study in Shizuoka, Japan. Int J Gynecol Cancer 2007; 17: 37-43
  • 25 Schmidt D, Ulrich U. Endometrioseassoziierte Tumorerkrankungen des Ovars. Pathologe 2014; 35: 348-354
  • 26 Sampson JA. Endometrial carcinoma of the ovary arising in endometrial tissue in that organ. Arch Surg 1925; 10: 1-72
  • 27 Scott RB. Malignant changes in endometriosis. Obstet Gynecol 1953; 2: 283-289
  • 28 Kim HS, Kim TH, Chung HH et al. Risk and prognosis of ovarian cancer in women with endometriosis: a meta-analysis. Br J Cancer 2014; 110: 1878-1890
  • 29 Heaps JM, Nieberg RK, Berek JS. Malignant neoplasms arising in endometriosis. Obstet Gynecol 1990; 75: 1023-1028
  • 30 Irvin W, Pelkey T, Rice L et al. Endometrial stromal sarcoma of the vulva arising in extraovarian endometriosis: a case report and literature review. Gynecol Oncol 1998; 71: 313-316
  • 31 Ulrich U, Rhiem K, Kaminski M et al. Parametrial and rectovaginal adenocarcinoma arising from endometriosis. Int J Gynecol Cancer 2005; 15: 1206-1209
  • 32 Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch 2012; 460: 237-249
  • 33 McCluggage WG. Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. Pathology 2011; 43: 420-432
  • 34 LaGrenade A, Silverberg SG. Ovarian tumors associated with atypical endometriosis. Hum Pathol 1988; 19: 1080-1084
  • 35 Fukunaga M, Nomura K, Ishikawa E et al. Ovarian atypical endometriosis: its close association with malignant epithelial tumours. Histopathology 1997; 30: 249-255
  • 36 Clement PB. The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects. Adv Anat Pathol 2007; 14: 241-260
  • 37 Seidman JD. Prognostic importance of hyperplasia and atypia in endometriosis. Int J Gynecol Pathol 1996; 15: 1-9
  • 38 Prefumo F, Todeschini F, Fulcheri E et al. Epithelial abnormalities in cystic ovarian endometriosis. Gynecol Oncol 2002; 84: 280-284
  • 39 Maiorana A, Cicerone C, Niceta M et al. Evaluation of serum CA 125 levels in patients with pelvic pain related to endometriosis. Int J Biol Markers 2007; 22: 200-202
  • 40 Worley MJ, Welch WR, Berkowitz RS et al. Endometriosis-associated ovarian cancer: a review of pathogenesis. Int J Mol Sci 2013; 14: 5367-5379
  • 41 Varma R, Rollason T, Gupta JK et al. Endometriosis and the neoplastic process. Reproduction 2004; 127: 293-304
  • 42 Somigliana E, Vigano P, Parazzini F et al. Association between endometriosis and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol 2006; 101: 331-341
  • 43 Yamaguchi K, Mandai M, Toyokuni S et al. 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 2008; 14: 32-40
  • 44 Pylvas M, Puistola U, Laatio L et al. Elevated serum 8-OHdG is associated with poor prognosis in epithelial ovarian cancer. Anticancer Res 2011; 31: 1411-1415
  • 45 Sato N, Tsunoda H, Nishida M 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
  • 46 Wiegand KC, Shah SP, Al-Agha OM et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 2010; 363: 1532-1543
  • 47 Esteller M, Catasus L, Matias-Guiu X et al. hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am J Pathol 1999; 155: 1767-1772
  • 48 Stewart CJ, Leung Y, Walsh MD et al. KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis. Hum Pathol 2012; 43: 1177-1183
  • 49 Shin JC, Ross HL, Elias S et al. Detection of chromosomal aneuploidy in endometriosis by multi-color fluorescence in situ hybridization (FISH). Hum Genet 1997; 100: 401-406
  • 50 Simpson JL, Bischoff FZ, Kamat A et al. Genetics of endometriosis. Obstet Gynecol Clin North Am 2003; 30: 21-40 vii
  • 51 Jiang X, Morland SJ, Hitchcock A et al. Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage. Cancer Res 1998; 58: 1707-1712
  • 52 Obata K, Hoshiai H. Common genetic changes between endometriosis and ovarian cancer. Gynecol Obstet Invest 2000; 50 (Suppl. 01) 39-43
  • 53 Martini M, Ciccarone M, Garganese G et al. Possible involvement of hMLH1, p 16(INK4 a) and PTEN in the malignant transformation of endometriosis. Int J Cancer 2002; 102: 398-406
  • 54 Nezhat F, Cohen C, Rahaman J et al. Comparative immunohistochemical studies of bcl-2 and p 53 proteins in benign and malignant ovarian endometriotic cysts. Cancer 2002; 94: 2935-2940
  • 55 Vigano P, Somigliana E, Chiodo I et al. Molecular mechanisms and biological plausibility underlying the malignant transformation of endometriosis: a critical analysis. Hum Reprod Update 2006; 12: 77-89
  • 56 Prowse AH, Manek S, Varma R et al. Molecular genetic evidence that endometriosis is a precursor of ovarian cancer. Int J Cancer 2006; 119: 556-562
  • 57 Kobayashi H, Sumimoto K, Kitanaka T et al. Ovarian endometrioma–risks factors of ovarian cancer development. Eur J Obstet Gynecol Reprod Biol 2008; 138: 187-193
  • 58 Zanetta GM, Webb MJ, Li H et al. Hyperestrogenism: a relevant risk factor for the development of cancer from endometriosis. Gynecol Oncol 2000; 79: 18-22
  • 59 Merritt MA, De Pari M, Vitonis AF et al. Reproductive characteristics in relation to ovarian cancer risk by histologic pathways. Hum Reprod 2013; 28: 1406-1417
  • 60 Aris A. Endometriosis-associated ovarian cancer: a ten-year cohort study of women living in the Estrie Region of Quebec, Canada. J Ovarian Res 2010; 3: 2
  • 61 Orezzoli JP, Russell AH, Oliva E et al. Prognostic implication of endometriosis in clear cell carcinoma of the ovary. Gynecol Oncol 2008; 110: 336-344
  • 62 Davis M, Rauh-Hain JA, Andrade C et al. Comparison of clinical outcomes of patients with clear cell and endometrioid ovarian cancer associated with endometriosis to papillary serous carcinoma of the ovary. Gynecol Oncol 2014; 132: 760-766
  • 63 Scarfone G, Bergamini A, Noli S et al. Characteristics of clear cell ovarian cancer arising from endometriosis: a two center cohort study. Gynecol Oncol 2014; 133: 480-484
  • 64 Boyraz G, Selcuk I, Yazicioglu A et al. Ovarian carcinoma associated with endometriosis. Eur J Obstet Gynecol Reprod Biol 2013; 170: 211-213
  • 65 Erzen M, Rakar S, Klancnik B et al. Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study. Gynecol Oncol 2001; 83: 100-108
  • 66 Melin A, Lundholm C, Malki N et al. Endometriosis as a prognostic factor for cancer survival. Int J Cancer 2011; 129: 948-955
  • 67 Kumar S, Munkarah A, Arabi H et al. Prognostic analysis of ovarian cancer associated with endometriosis. Am J Obstet Gynecol 2011; 204: 63.e1-63.e7
  • 68 Moen MH, Rees M, Brincat M et al. EMAS position statement: Managing the menopause in women with a past history of endometriosis. Maturitas 2010; 67: 94-97
  • 69 Soliman NF, Hillard TC. Hormone replacement therapy in women with past history of endometriosis. Climacteric 2006; 9: 325-335
  • 70 Van Gorp T, Amant F, Neven P et al. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Pract Res Clin Obstet Gynaecol 2004; 18: 349-371
  • 71 Ulrich U, Richter O, Wardelmann E et al. [Endometriosis and malignoma]. Zentralbl Gynakol 2003; 125: 239-242