Subscribe to RSS
DOI: 10.1055/s-2002-20315
© Georg Thieme Verlag Stuttgart · New York
Präkanzeröse Läsionen des Endometriums und Veränderungen unter Tamoxifen-Therapie
Precancerous Lesion of the Endometrium and Endometrial Morphology in Patients with Tamoxifen TherapyPublication History
Publication Date:
25 February 2002 (online)
![](https://www.thieme-connect.de/media/zblgyn/200201/lookinside/thumbnails/10.1055-s-2002-20315-1.jpg)
Zusammenfassung
Endometrioide Karzinome (Typ-1-Karzinome) sind östrogenabhängig und oft mit endometrialen Hyperplasien assoziiert. Die Nomenklatur dieser Hyperplasien ist derzeit im Fluss. Die schwere adenomatöse Hyperplasie (atypische Hyperplasie) ist eine obligate Präkanzerose und bedarf in der Postmenopause der Hysterektomie. Die anderen histologischen Typen des Endometriumkarzinoms, das serös-papilläre und das klarzellige (sog. Typ-2-Karzinome) Karzinom zeigen keine gleichartige Assoziation zu Vorläuferläsionen und sind nicht östrogenabhängig. Bei endometrialen Veränderungen unter Tamoxifen-Therapie stehen die Atrophie und der Nachweis fibrös-zystischer Polypen, mit und ohne zelluläre Metaplasien, im Vordergrund. Bei denen mit der Therapie assoziierten Karzinomen stellt sich die Frage, ob sie nicht auf einem bereits zuvor östrogenstimulierten Endometrium entstanden sind.
Summary
The endometrioid type of endometrial adenocarcinoma „(type 1-carcinoma) is estrogen-dependend and frequently associated with endometrial hyperplasia. The nomenclature of these hyperplasias is currently under discussion. The highest risk for metachronous carcinoma is associated with atypical hyperplasia of the endometrium as detected in fractional curettings. In postmenopausal patients treatment should consist of abdominal hysterectomy. The so-called type 2-carcinomas, serous-papillary and clear-cell type, do not demonstrate a similar association with precursor lesions. Pathological findings in patients treated with Tamoxifen include endometrial atrophy and fibro-cystic endometrial polyps, sometimes with cellular metaplasias. Patients with breast cancer and tamoxifen treatment have an increased risk of endometrial carcinoma. In some of these patients it could be argued whether the carcinoma has developed in a preceeding endometrial hyperplasia.
Schlüsselwörter
Endometrium - Hyperplasie - Karzinom - Pathogenese - Tamoxifen
Key words
Endometrium - Hyperplasia - Carcinoma - Pathogenesis - Tamoxifen
Literatur
- 1 Baak J PA, Wisse-Brekelmans E CM, Fleege J C, van der Putten H WHM, Bezemer P D. Assessment of the risk on endometrial cancer in hyperplasia by means of morphological and morphometrical features. Path Res Pract. 1992; 188 856-859
- 2 Bastert G, Beckmann M W, Blohmer J U, Dallenbach-Hellweg G, Dunst J, Emons G, Friese K, Grischke E M, Horn L C, Kleine W, Kurbacher C, Junkermann H, Mahlke M, Melsheimer P, Pichl H, Schneider A, Schulz K D, Wagner U, Wallwiener D. Kurzgefasste interdisziplinäre AGO-Leitlinien für die Diagnostik und Therapie des Endometriumkarzinoms. Zentralbl Gynakol. 2002; 124 58-62
- 3 Beckmann M W, Hanstein B, Niederacher D, Jap D, Kuschel B, Bender H G. Wirkmechanismen ovarieller Steroidhormone und Antiöstrogene in der Karzinogenese der Mamma und des Endometriums. Geburtshilfe Frauenheilk. 2000; 60 71-76
- 4 Bergeron C, Nogales F F, Masseroli M, Abeler V, Duvillard P, Müller-Holzner E, Pickartz H, Wells M. A multicentric european study testing the reproducibility of the WHO classification of endometrial hyperplasia with a proposal of a simplified Working Classification for biopsy and curettage specimens. Am J Surg Pathol. 1999; 23 1102-1108
- 5 Boakman J B, Maximov S J. Relative risk of development and active detection of primary multiple endometrial, breast and ovarian cancer. Eur J Gynecol Oncol. 1993; 14 114-118
- 6 Bokhman J V. Two pathogenic types of endometrial carcinoma. Gynecol Oncol. 1983; 15 10-17
- 7 Burton J L, Wells M. Recent advances in the histopathology and molecular pathology of carcinoma of the endometrium. Histopathology. 1998; 33 297-303
- 8 Cardosi R J, Fiorica J V. Surveillance of the endometrium in tamoxifen treated women. Curr Opin Obstet Gynecol. 2000; 12 27-31
- 9 Dallenbach-Hellweg G, Hahn U, Schmidt D. Morphologische Endometriumveränderungen unter Tamoxifen. Zentralbl Gynakol. 1996; 118 365-369
- 10 Dallenbach-Hellweg G, Schmidt D, Hellberg P, Bourne T, Kreuzwieser E, Dören M, Rydh W, Rudenstam G, Granberg S. The endometrium in breast cancer patients on tamoxifen. Arch Gynecol Obstet. 2000; 263 170-177
- 11 Dallenbach-Hellweg G, Schmidt D. Oestrogens and proliferation of endometrial cells. J Cardiol Pharmacol. 1996; 28 (Suppl 5) 24-28
- 12 Deligdisch L, Kalir T, Cohen C J, de Latour M, Le Bouedec G, Penault-Lorca F. Endometrial histopathology in 700 patients treated with tamoxifen for breast cancer. Gynecol Oncol. 2000; 78 181-186
- 13 Enomoto T, Inoue M, Perantoni A O. et al . K-ras activation in permaligant and malignant epithelial lesions of the human uterus. Cancer Res. 1991; 51 5308-5314
- 14 Gerber B, Kraues A, Müller H, Reimer T, Külz T, Makovitzky J, Kundt G, Friese K. Effects of adjuvant Tamoxifen on the endometrium in postemnopausal women with breats Cancer: Prospective long-term study using transvaginal ultrasound. J Clin Oncol. 2000; 18 3464-3470
- 15 Hanstein B, Beckmann M W, Bender H G. Charakterisierung und Bedeutung verschiedener Östrogenrezeptortypen unter besonderer Berücksichtigung des Endometriumkarzinoms. Zentralbl Gynakol. 2002; 124 17-19
- 16 Hendrickson M R, Ross J C, Kempson R L. Toward the development of morphologic criteria for well differentiated adenocarcinoma of the endometrium. Am J Surg Pathol. 1983; 7 819-821
- 17 Horn L C, Bilek K, Schnurrbusch U. Endometriale Hyperplasien: Histologie, Klassifikation, prognostische Bedeutung und Therapie. Zentralbl Gynäkol. 1997; 119 251-259
- 18 Horn L C, Lax S F, Höckel M, Fischer U, Schmidt D. Präkanzeröse Läsionen des Endometriums: Aspekte der molekularen Pathogenese und Probleme der Nomenklatur. Geburtsh Frauenheilk. 2001 a; 61 8-14
- 19 Horn L C, Schnurrbusch U, Bilek K, Einenkel J. Karzinomrisiko endometrialer Hyperplasien: Eine kliniko-pathologische Analyse von 538 Fällen. Geburtsh Frauenheilk. 2001; 61 501-506
- 20 Kendall B S, Ronnet B M, Isacson C, Cho K R, Hedrick L, Diener-West M, Kurman R J. Reproducibility of the diagnosis of endometrial hyperplasia, atypical hyperplasia and well differentiated carcinoma. Am J Surg Pathol. 1998; 22 1012-1019
- 21 Kommoss F, Karck U, Prömpeler H, Pfisterer J, Kirkpatrick C J. Steroid receptor expression in endometria from women treated with tamoxifen. Gynecol Oncol. 1998; 70 188-191
- 22 Kurman R J, Kaminski P F, Norris H J. The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer. 1985; 56 403-412
- 23 Kurman R J, Norris H J. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer. 1982; 49 2547-2559
- 24 Lax S F. Molekulare Pathogenese des Endometriumkarzinoms. Zentralbl Gynakol. 2002; 124 10-16
- 25 Levine R L, Cargile C B, Blazes M S, Van Rees B, Kurman R J, Ellenson L H. PTEN mutations and microsatellite instability in complex atypical hyperplasia, a precursor lesion to uterine endometrioid carcinoma. Cancer Res. 1998; 58 3254-3258
- 26 Longacre T A, Chung M H, Jensen D N, Hendrickson M R. Proposed criteria for the diagnosis of well-differentiated endometrial carcinoma. A diagnostic test for myoinvasion. Am J Surg Pathol. 1995; 19 371-406
- 27 Magriples U, Naftolin F, Schwartz P E, Carcangiu M L. High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients. J Clin Oncol. 1993; 11 485-490
- 28 Mutter G L and. The Endometrial Collaborative Group . Endometrial intraepithelial neoplasia (EIN): Will it bring order to chaos?. Gynecol Oncol. 2000; 76 287-290
- 29 Mutter G L, Lin M C, Fitzgerald J T, Kum J B, Baak J PA, Lees J, Weng L P, Eng C. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000; 92 924-930
- 30 Mutter G L, Ince T A, Baak J P, Kust G A, Zhou X P, Eng C. Molecular identification of latent precancers in histologically normal Endometrium. Cancer Res. 2001; 61 4311-4314
- 31 Randall T C, Kurman R J. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol. 1997; 90 434-440
- 32 Rutquist L E, Johansson H, Signomklao T. Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group. J Natl Cancer Inst. 1995; 87 645-651
- 33 Sasaki H, Nishii H, Tada A. Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma. Cancer Res. 1993; 53 1906-1910
- 34 Schulze-Mosgau A, Montzka P, Krüger S, Bauer O, Ortmann O, Diedrich K. Zur Prävalenz von hyperplastischen und neoplastischen Veränderungen des Endometriums bei postmenopausalen Patientinnen mit Mammakarzinom unter Tamoxifentherapie. Geburtsh Frauenheilk. 1999; 59 606-615
- 35 Scully R E, Bonfiglio T A, Kurman R J, Silverberg S G, Wilkinson E J. WHO-Histological typing of female genital tract tumours. Springer, Berlin, Heidelberg, New York 1994
- 36 Scully R E, Young R H. Endometrioid neoplasia retrogressive terminology. (Letter to the editor). Am J Surg Pathol. 2000; 24 753-754
- 37 Skov B G, Broholm H, Engel U, Franzmann M B, Nielsen A L, Lauritzen A F, Skov T. Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of endometrial hyperplasia. Int J Gynecol Pythol. 1997; 16 33-37
- 38 Susini T, Massi D, Paglierani M, Nasciullo V, Scambia G, Giordano A, Amunni G, Massi G, Taddei G L. Expression of the retinoblastoma-related gene RB2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma. Hum Pathol. 2001; 32 360-367
Prof. Dr. Dr. h. c. Dietmar Schmidt
Institut für Pathologie
Referenzzentrum für Gynäkopathologie
A 2,2
D-68159 Mannheim
Phone: 0621-2 27 79
Fax: 0621-15 32 88
Email: dietmar.schmidt@dgn.de