Endometriose und Malignom

Zusammenfassung

Maligne Tumoren auf dem Boden einer Endometriose sind selten. Sie treten in etwa 1 % der Fälle auf, wovon 80 % auf das Ovar und 20 % auf extragonadale Manifestationen entfallen. Häufigste extragonadale Manifestationen sind das Rektosigmoid und das Septum rectovaginale. Die Therapie von extragonadalen Endometriose-assoziierten Karzinomen besteht in der Resektion möglichst im Gesunden mit postoperativer Radiatio, ggf. mit adjuvanter Gestagengabe. Endometriose- assoziierte Ovarialkarzinome präsentieren sich häufiger in früheren Stadien und häufiger mit G1-und G2-Differenzierung. Sie werden wie Ovarialkarzinome behandelt, wobei ein schlechteres Ansprechen auf eine Chemotherapie angenommen wird. Da eine Östrogenmonotherapie ein potenzieller Risikofaktor für das Auftreten von Endometriose-assoziierten Malignomen ist, wird sie bei positiver Anamnese für Endometriose als Hormonersatz in der Peri- und Postmenopause nicht empfohlen. Heterozygotieverlust und Mutationen des PTEN Tumorsuppressorgens könnten frühe Ereignisse der Malignisierung sein. Möglicherweise sind die Endometriose und ihre maligne Transformation ein geeignetes Modell zum Studium der Krebsentstehung. Endometriose ist nach aktuellen Studien mit einem etwas erhöhten relativen Risiko, an einem Non-Hodgkin-Lymphom zu erkranken, assoziiert.

Abstract

Malignant tumors arising from endometriosis are rare. A frequency of about 1 % has been reported with in 80 % the ovary, and in 20 % extragonadal sites being affected. The most common extragonadal manifestations are the rectosigmoid and the rectovaginal septum. For extragonadal malignant tumors arising from endometriosis, complete resection followed by post-operative radiotherapy, possibly plus adjuvant progestin therapy, is the treatment of choice. Endometriosis-associated ovarian carcinomas are likely to present with lower stage disease and predominantly lower grade tumors. While their treatment follows that of common ovarian cancer, a poorer response to chemotherapy must be considered. As unopposed estrogen replacement therapy has been identified as a risk factor for the development of endometriosis-associated cancer, it is not recommended for hormone replacement therapy in women with a history of endometriosis. Loss of heterozygosity and mutations of the PTEN tumor suppressor gene may be early events of tumorigenesis. Endometriosis and its malignant transformation, perhaps, may serve as a suitable model in this regard. According to recent studies, endometriosis is associated with an increased relative risk of non-Hodgkin lymphoma.

Schlüsselwörter

Endometriose - Kanzerisierung endometriose-assoziiert - Ovarialkarzinom - PTEN Tumorsuppressorgen - Non-Hodgkin-Lymphom

Key words

Endometriosis - tumorigenesis - ovarian cancer - PTEN tumor supressor gene - non-Hodgkin lymphoma

Literatur

• 1 Addison W A, Hammond C B, Parker R T. The occurence of adenocarcinoma in endometriosis of the rectovaginal septum during progestational therapy.  Gynecol Oncol. 1979;  8 193-197
• 2 Aslani M, Scully R E. Primary carcinomas of the broad ligament. Report of four cases and review of the literature.  Cancer. 1989;  64 1540-1545
• 3 Berger A, Rouzier R, Carnot F, Braunberger E, Cugnenc P -H, Danel C. Primary adenocarcinoma of the rectovaginal septum: a case report and literature review.  Eur J Obstet Gynecol Reprod Biol. 2001;  95 111-113
• 4 Bischoff F Z, Simpson J L. Heritability and molecular genetic studies of endometriosis.  Hum Reprod Update. 2000;  6 37-44
• 5 Brinton L A, Gridley G, Persson I, Baron J, Bergqvist A. Cancer risk after a hospital discharge diagnosis of endometriosis.  Am J Obstet Gynecol. 1997;  176 572-579
• 6 Brooks J J, Wheeler J E. Malignancy arising in extragonadal endometriosis.  Cancer. 1977;  40 3065-3073
• 7 Brunson G L, Barclay D L, Sanders M, Aroaz C A. Malignant extraovarian endometriosis: two case reports and review of the literature.  Gynecol Oncol. 1988;  30 123-130
• 8 Erzen M, Rakar S, Klancnik B, Syrjanen K, Klancar B. Endometriosis- associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by nested case-control study.  Gynecol Oncol. 2001;  83 100-108
• 9 Goldberg M I, Belinson J L, Hutson E D, Nordqvist S R. Clear cell carcinoma arising in endometriosis of the rectovaginal septum.  Obstet Gynecol. 1978;  51 (Suppl) 38-40
• 10 Han A C, Hovenden S, Rosenblum N G, Salazar H. Adenocarcinoma arising in extragonadal endometriosis: an immunohistological study.  Cancer. 1998;  83 1163-1169
• 11 Haskel S, Chen S S, Spiegel G. Vaginal endometrioid adenocarcinoma arising in vaginal endometriosis: a case report and literature review.  Gynecol Oncol. 1989;  34 232-236
• 12 Heaps J M, Nieberg R K, Berek J S. Malignant neoplasms arising in endometriosis.  Obstet Gynecol. 1990;  75 1023-1028
• 13 Hitti I F, Glasberg S S, Lubicz S. Clear cell carcinoma arising in extraovarian endometriosis: report of three cases and review of the literature.  Gynecol Oncol. 1990;  39 314-320
• 14 Jones K D, Owen E, Berresford A, Sutton C. Endometrial adenocarcinoma arising from endometriosis of the rectosigmoid colon.  Gynecol Oncol. 2002;  86 220-222
• 15 Martini M, Ciccarone M, Garganese G, Maggiore C, Evangelista A, Rahimi S, Zannoni G, Vittori G, Larocca L M. Possible involvement of hMLH1, p16 (INK4a) and PTEN in the malignant transformation of endometriosis.  Int J Cancer. 2002;  102 398-406
• 16 McCluggage W G, Bryson C, Lamki H, Boyle D D. Benign, borderline, and malignant endometrioid neoplasia arising in endometriosis in association with tamoxifen therapy.  Int J Gynecol Pathol. 2000;  19 276-279
• 17 Modesitt S C, Tortolero- Luna G, Robinson J B, Gershenson D M, Wolf J K. Ovarian and extraovarian endometriosis-associated cancer.  Obstet Gynecol. 2002;  100 788-795
• 18 Mostoufizadeh M GH, Scully R E. Malignant tumors arising in endometriosis.  Clin Obstet Gynecol. 1980;  23 951-954
• 19 Nishida M, Watanabe K, Sato N, Ichikawa Y. Malignant transformation of ovarian endometriosis.  Gynecol Obstet Invest. 2000;  50 (Suppl 1) 18-25
• 20 Obata K, Morland S J, Watson R H, Hitchcock A, Chenevix-Trench O, Thomas E J, Campbell I G. Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors.  Cancer Res. 1998;  58 2095-2097
• 21 Olson J E, Cerhan J R, Janney C A, Anderson K E, Vachon C M, Sellers T A. Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women's Health Study.  Cancer. 2002;  94 1612-1618
• 22 Reimnitz C, Brand E, Nieberg R K, Hacker N F. Malignancy arising in endometriosis associated with unopposed estrogen replacement.  Obstet Gynecol. 1988;  71 444-447
• 23 Sainz de la Cuesta R, Eichhorn J H, Rice L W, Fuller AF A F, Nikrui N, Goff B A. Histologic transformation of benign endometriosis to early epithelial ovarian cancer.  Gynecol Oncol. 1996;  60 238-244
• 24 Sampson J A. Endometrial carcinoma of ovary rising in endometrial tissue in that organ.  Arch Surg. 1925;  10 1-72
• 25 Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T, Noguchi M. Loss of heterozygosity on 10q23.3 and mutations of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometriosis cyst to endometrioid carcinoma and clear cell carcinoma of the ovary.  Cancer Res. 2000;  60 7052-7056
• 26 Sillem M, Prifti S, Monga B, Buvari P, Shamia U, Runnebaum B. Soluble urokinase-type plasminogen activator receptor is over-expressed in uterine endometrium from women with endometriosis.  Mol Hum Reprod. 1997;  3 1101-1105
• 27 Slavin R E, Krum R, Van Dinh T. Endometriosis- associated intestinal tumors: a clinical and pathological study of 6 cases with a review of the literature.  Hum Pathol. 2000;  31 456-463
• 28 Stern R C, Dash R, Bentley R C, Snyder M J, Haney A F, Robboy S J. Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types.  Int J Gynecol Pathol. 2001;  20 133-139
• 29 Swiersz L M. Role of endometriosis in cancer and tumor development.  Ann NY Acad Sci. 2002;  955 281-292
• 30 Ulrich U, Sillem M, Keckstein J. Endometriose: medikamentöse und chirurgische Therapie.  Med Welt. 2002;  53 23-28
• 31 Yantiss R K, Clement P B, Young R H. Neoplastic and pre-neoplastic changes in gastrointestinal endometriosis: a study of 17 cases.  Am J Surg Pathol. 2000;  24 513-524
• 32 Young E F, Gamble C N. Primary adenocarcinoma of the rectovaginal septum arising in endometriosis. Report of a case.  Cancer. 1969;  24 597-601