Aktuelle Aspekte des Endometriumkarzinoms[*]

Zusammenfassung

Mittlerweile ist das Endometriumkarzinom das häufigste Malignom der weiblichen Genitalien. Pathogenetisch lassen sich 2 Typen unterscheiden: der klassische östrogeninduzierte endometriale und der nichtklassische hormonunabhängige seröse Typ. Die adenomatöse Hyperplasie als Präkanzerose zu identifizieren, ist bisher in hohem Maße an subjektive Kriterien gebunden und dementsprechend wenig reproduzierbar. Eine Verbesserung mittels morphometrischer und molekulargenetischer Methoden erscheint hilfreich. Für die Diagnose des Endometriumkarzinoms ist nach wie vor die fraktionierte Kürettage der Goldstandard. Die Differenzialdiagnose zwischen einem Adenokarzinom des Endometriums und der Endozervix lässt sich durch eine Kombination von Antikörpern immunhistochemisch abklären. Der Eckpfeiler der Therapie ist die Operation, wobei eine differenzierte individuelle Entscheidung je nach histologischem Befund bedeutsam ist. Zunehmend umstritten ist die postoperative adjuvante Radiatio, während die Brachytherapie der Vagina mittlerweile als etabliert gilt. Der vorliegende Artikel vermittelt einen Überblick über die aktuelle Situation der Pathogenese, Diagnose und Therapie des Endometriumkarzinoms.

Abstract

The endometrial carcinoma is meanwhile the most common malignant tumor of the female genital tract. 2 subtypes can be divided according the pathogenesis: the classical estrogen related endometroid type and the nonclassical estrogen unrelated serous type. The endometrial adenomatous hyperplasia as a precancerous lesion must be identified by subjective criteria. Therefore the histological diagnosis is worse reproducible. An improvement would be helpful by morphometric and moleculargenetic methods. The golden standard of diagnosis of the endometrial carcinoma is fractional dilatation and curettage. Immunohistochemical staining with a limited panel of antibodies can discriminate between an endometrial and an endocervical origin of an adenocarcinoma. The corner stone of the therapy is surgery. An individual decision about postoperative treatment is very important and depends on histological criteria. The adjuvant postoperative whole pelvic radiation is under discussion whereas the vaginal brachytherapy is established as standard therapy. This article outlines an overview of the actual situation for pathogenesis, diagnosis and treatment endometrial cancer.

Schlüsselwörter

Endometriumkarzinom - Pathogenese - Diagnose - Therapie

Keywords

Endometrial carcinoma - pathogenesis - diagnosis - therapy

1 Auszugsweise vorgetragen am 23. 02. 2002 anlässlich „Gynäkologie und Geburtshilfe, Frankfurt, 2002”

Literatur

• 1 Aalders J, Abeler V, Kolstad P, Onsrud M. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients.  Obstet Gynecol. 1980;  56 419-427
• 2 Arikan G, Reich O, Weiss U, Hahn T, Reinisch S, Tamussino K, Pickel M, Desoye G. Are endometrial carcinoma cells disseminated at hysteroscopy functionally viable?.  Gynecol Oncol. 2002;  83 221-226
• 3 Ben-Yehuda O M, Kim Y B, Lendter R S. Does hysteroscopy improve on the sensitivity of dilatation and curettage in the diagnosis of endometrial hyperplasia or carcinoma?.  Gynecol Oncol. 1998;  68 4-7
• 4 Bergeron C, Nogades F F, Masseroli M, Abeler V, Duvillard P, Müller-Holzner E, Pichartz 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 of biopsy and curettage specimens.  Am J Surg Pathol. 1999;  23 1102-1108
• 5 Boente M P, Yordan E L, McIntosh D G, Grendys E C, Orandi Y A, Davies S, Beck D, Graham J E, Miller A, Marshall R, Dolan T, Kirschner C, Reddy S, Wilbanks G D. Prognostic factors and long-term survival in endometrial adenocarcinoma with cervical involvement.  Gynecol Oncol. 1993;  51 316-322
• 6 Boente M P, Orandi Y A, Yordan E L, Miller A, Graham J E, Kirshner C, Wilbanks G D. Recurrence patterns and complications in endometrial adenocarcinoma with cervical involvement.  Am Surg Oncol. 1995;  2 138-144
• 7 Bokhman J V. Two pathogenetic types of endometrial carcinoma.  Gynecol Oncol. 1983;  15 10-17
• 8 Boronow R. Surgical staging of endometrial cancer: evolution, evaluation and responsible challenge - a personal perspective.  Gynecol Oncol. 1997;  66 179-189
• 9 Castrillon D H, Lee K R, Nucci M R. Distinction between endometrial and endocervical adenocarcinoma: an immunohistological study.  Int J Gynecol Pathol. 2002;  21 4-10
• 10 Cheng W, Lin H, Toung P, Huang S. Comparison of endometrial changes among symptomatic Tamoxifen-treated and nontreated perimenopausal and postmenopausal breast cancer patients.  Gynecol Oncol. 1997;  66 233-237
• 11 Cornelison T L, Trimble E L, Kosary C L. SEER data, corpus uteri cancer: treatment trends versus survival for FIGO stage II; 1988-1994.  Gynecol Oncol. 1999;  74 350-355
• 12 Creasman W T, De Geest K, Di Saia P J, Zaino P J. Significance of true surgical pathology staging: a Gynecologic Group study.  Am J Obstet Gynecol. 1999;  181 31-34
• 13 Creutzberg L L, van Putten W L, Koper P, Lybeert M J, Jobsen J, Warlam-Rodenhuis C C, de Winter K A, Lutgens L C, van-den Bergh L, van de Steen-Banasik E, Beerman H, van Lent M. Surgery and post-operative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomized trial.  Lancet. 2000;  355 1404-1411
• 14 Dallenbach-Hellweg G, Schmidt D. Distinction between endometrial and endocervical adenocarcinoma.  Int J Gynecol Pathol. 2002;  21 307-308
• 15 Dietl J. Das Lymphknotenproblem in der Frauenheilkunde.  Geburtsh Frauenheilk. 1999;  59 589-598
• 16 Dietl J, Stoll P. Zur Effizienz der Früherkennung des Endometriumkarzinoms durch die endouterine Zellentnahme mit der Mi-Mark-Spirale.  Geburtsh Frauenheilk. 1985;  45 299-301
• 17 Duska L R, Garrett A, Rueda B R, Haas J, Chang Y, Fuller A F. Endometrial cancer in women 40 years old and younger.  Gynecol Oncol. 2001;  83 388-393
• 18 Egarter C, Krestan C, Kurz C. Abdominal dissemination of malignant cells with hysteroscopy.  Gynecol Oncol. 1996;  63 143-144
• 19 Ellenson L H. II. the molecular biology of endometrial tumorigenesis : does it have a message?.  Int J Gynecol Pathol. 2000;  19 310-313
• 20 Eltabbakh G H, Moore A D. Survival of women with surgical stage II endometrial cancer.  Gynecol Oncol. 1999;  74 80-85
• 21 Evans-Metcalf E R, Brooks S E, Reale F R, Baker S P. Profile of women 45 years of age and younger with endometrial cancer.  Obstet Gynecol. 1998;  91 349-354
• 22 Fanning J. Long term survival of intermediate risk endometrial cancer (stage I G₂, I_c, II) treated with full lymphadenectomy and brachytherapy without teletherapy.  Gynecol Oncol. 2001;  82 371-374
• 23 Fanning J, Nanavati P J, Hilgers R D. Surgical staging and high dose rate brachytherapy for endometrial cancer: limiting radiotherapy of node-positive tumors.  Obstet Gynecol. 1996;  87 1041-1044
• 24 Feldman S, Clapter A, Welch W, Berkowitz R S. The year follow-up of 263 patients with post/perimenopausal women vaginal bleeding and negative initial biopsy.  Gynecol Oncol. 1994;  55 56-59
• 25 Feltmate C M, Duska L R, Chang Y, Flynn C E, Nikrini N, Kiggunden E, Goodman A, Fuller A F, McIntyre J E. Predictors of recurrence in surgical stage II endometrial adenocarcinoma.  Gynecol Oncol. 1999;  73 407-411
• 26 Gibson L E, Barakat R R, Ven Katraman E S, Hoskins W J. Endometrial pathology at dilatation and curettage in breast cancer patients: comparison of Tamoxifen users and nonusers.  Cancer J Sci Am. 1996;  2 35-38
• 27 Gitsch G, Hanzal E, Jenson D, Hacker N F. Endometrial cancer in premenopausal women 45 years and younger.  Obstet Gynecol. 1995;  85 504-508
• 28 Grimes D A. Diagnostic dilatation and curettage: a reappraisal.  Am J Obstet Gynecol. 1982;  142 1-6
• 29 Gucer F, Tamussino K, Moser F, Arikan G, Winter R. Two-year follow-up of patients with endometrial carcinoma after preoperative fluid hysteroscopy.  Int J Gynecol Cancer. 1998;  8 476-480
• 30 Guido R S, Kanbour-Shakir A, Rubin M C, Christopherson W A. Pipelle endometrial sampling: sensitivity in the detection of endometrial cancer.  J Reprod Med. 1995;  40 553-555
• 31 Haenggi W, Gasser A, Feyereisl J, Maibach R, Spoerri S, Greiner R, Dreher E. Curative treatment of clinical stage II endometrial carcinoma.  Zentralbl Gynäkol. 1995;  117 207-212
• 32 Horowitz N S, Petus W A, Smith M M, Drescher C W, Atwood M, Mate T. Adjuvant high dose rate vaginal brachytherapy as treatment of stage I and II endometrial carcinoma.  Obstet Gynecol. 2002;  99 235-240
• 33 Kamoi S, AlJuboury M I, Akin M-R, Silverberg S G. Immunohistochemical staining in the distinction between primary endometrial and endocervical adenocarcinomas: another viewpoint.  Int J Gynecol Pathol. 2002;  21 217-223
• 34 Karlsson B, Crauberg S, Wickland M, Ylöstalo P, Torvid K, Marsal K, Valentin L. Transvaginal ultrasonography of the Endometrium in women with postmenopausal bleeding - a Nordic multicenter study.  Am J Obstet Gynecol. 1995;  172 1488-1494
• 35 Kendall B S, Ronnett B M, Isaeson 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
• 36 Kim Y B, Holschneider C H, Ghosh K, Nieberg R K, Montz F J. Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature.  Cancer. 1997;  79 320-327
• 37 Kimmig R, Strowitzki T, Müller-Hocker J, Kürzl R, Korell M, Hepp H. Conservative treatment of endometrial cancer permitting subsequent triplet pregnancy.  Gynecol Oncol. 1995;  58 255-257
• 38 Krauß T, Huschmand H, Hinney B, Viereck V, Emons G. Hormon- und Chemotherapie beim Endometriumkarzinom.  Zentralbl Gynaekol. 2002;  124 45-50
• 39 Kurman R J. Introduction to the ISGYP symposium on endometrial hyperplasia.  Int J Gynecol Pathol. 2000;  19 299-300
• 40 Larson D M, Broste S K, Krawisz B R. Surgery without radiotherapy for primary treatment of endometrial Cancer.  Obstet Gynecol. 1998;  91 355-359
• 41 Lax S F. Molekulare Pathogenese des Endometriumkarzinoms auf Basis eines dualistischen Modells.  Zentralbl Gynäkol. 2002;  124 10-16
• 42 Le T D, Yamada S D, Rutgers J L, Di Saia P J. Complete response of a stage IV uterine papillary serous carcinoma to neoadjuvant chemotherapy with Taxol and carboplatin.  Gynecol Oncol. 1999;  73 461-463
• 43 Lybeert M L, van Putten W L, Brolmann H A, Coebergh J W. Postoperative radiotherapy for endometrial carcinoma stage I. Wide variation in referral patterns but no effect on long-term survival in a retrospective study in the southeast Netherlands.  Eur J Cancer. 1998;  34 586-590
• 44 Mariani A, Webb M J, Keeney G L, Calori G, Podratz K C. Role of wide/ radical hysterectomy and pelvic lymph node dissection in endometrial cancer with cervical involvement.  Gynecol Oncol. 2001;  83 72-80
• 45 Mc Cluggage W G, Sumathi V P, Mc Bride H A, Patterson A. A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptors, aids the distinction between primary endometrial and endocervical adenocarcinomas.  Int J Gynecol Pathol. 2002;  21 11-15
• 46 Macdonald R R, Thorogood J, Mason M K. A randomized trial of progestogens in the primary treatment of endometrial carcinoma.  Br J Obstet Gynaecol. 1988;  95 166-174
• 47 Morrow C P, Bundy B N, Homesley H D, Creasman W T, Hornback N B, Kurman R, Thigpen J T. Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: a Gynaecologic Oncology Group Study.  Gynecol Oncol. 1990;  36 166-171
• 48 Morrow C P, Bundy B N, Kurman R J, Creasman W T, Heller P, Homesley H D, Graham J E. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the Endometrium: a Gynecologic Oncology Group study.  Gynecol Oncol. 1991;  40 55-65
• 49 Mutter G L. Histopathology of genetically defined endometrial precancers.  Int J Gynecol Pathol. 2000;  19 301-309
• 50 Mutter G L. Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? The Endometrial Collaborative Group.  Gynecol Oncol. 2000;  76 287-290
• 51 Ng T J, Nicklin J L, Perrin L C, Chenk R, Crandon A J. Postoperative vaginal vault brachytherapy for node-negative stage II (occult) endometrial carcinoma.  Gynecol Oncol. 2001;  81 193-195
• 52 Ng T Y, Perrin L C, Nicklin J L, Chenk R, Crandon A J. Local recurrence in high-risk node-negative stage I endometrial carcinoma treated with postoperative vaginal vault brachytherapy.  Gynecol Oncol. 2000;  79 490-494
• 53 Orr J W. Surgical staging of endometrial cancer: does the patient benefit?.  Gynecol Oncol. 1998;  71 335-339
• 54 Orr J W, Holimon J L, Orr P F. Stage I corpus cancer: Is teletherapy necessary?.  Am J Obstet Gynecol. 1997;  176 777-789
• 55 Pecorelli S. FIGO Annual report on the result of treatment in gynaecological cancer, 23^rd ed.  J Epidemiol Biostat. 1998;  3 1-168
• 56 Podratz K C, Mariani A, Webb M J. Staging and therapeutic value of lymphadenectomy in endometrial cancer.  Gynecol Oncol. 1998;  70 163-164
• 57 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
• 58 Roberts J A, Brunetto V L, Keys H M, Zaino R, Spiritos N M, Blass J D, Pearlman A, Mainan M A, Bell J G. A phase III randomized study of surgery vs surgery plus adjunctive radiation therapy in intermediate-risk endometrial adenocarcinoma.  Proc Soc Gynecol Oncol. 1998;  29 70
• 59 Rogerson L, Downes E. How do UK gynaecologists manage endometrial carcinoma? A national survey.  Eur J Gynaecol Oncol. 1998;  19 331-332
• 60 Rose P G. Endometrial carcinoma.  N Engl J Med. 1996;  335 640-649
• 61 Salvesen H B, Stefansson I, Kalvenes M B, Das S, Akslen L A. Loss of PTEN expression is associated with metastatic disease in patients with endometrial carcinoma.  Cancer. 2002;  94 2185-2191
• 62 Schmidt D, Horn L-C. Präkanzeröse Läsionen des Endometriums und Veränderungen unter Tamoxifen-Therapie.  Zentralbl Gynäkol. 2002;  124 3-9
• 63 Schmidt T, Römer Th. Sonographie und Hysteroskopie beim Endometriumkarzinom und seinen Vorstufen.  Zentralbl Gynäkol. 2002;  124 20-26
• 64 Scully R E, Bonfiglio T A, Kurman R J, Silverberg S G, Wilkinson E J. WHO-International Histological Classification of Tumours. Histological Typing of Female Genital Tract Tumours. 2nd ed. Springer-Verlag, New York 1994
• 65 Seago P D, Raman A, Shashikant L. Potential benefit of lymphadenectomy for the treatment of node-negative locally advanced uterine cancers.  Gynecol Oncol. 2001;  83 282-285
• 66 Sherman M E. Theories of endometrial carcinogenesis: a multidisciplinary approach.  Mod Pathol. 2000;  13 295-308
• 67 Stovall T G, Ling F W, Morgan P L. A prospective, randomised comparison of the Pipelle endometrial sampling device with the Novak curette.  Am J Obstet Gynecol. 1991;  165 1287-1290
• 68 Straughn M J, Huch W K, Kelly F J, Leath C A, Kleinberg M J, Hyde J, Numnum T M, Zhang Y, Soong S-J, Austin J M, Patridge E E, Kilgore Ö C, Alvarez R D. Conservative management of stage I endometrial carcinoma after surgical staging.  Gynecol Oncol. 2002;  84 194-200
• 69 Townsend D E, Fields G, Mc Camland A, Lauffman K. Diagnostic and operative hysteroscopy in the management of persistent postmenopausal bleeding.  Obstet Gynecol. 1993;  82 419-424
• 70 Vergote J, Kjorstad K, Abeler V, Kolstad P. A randomized trial of adjuvant progestagen in early endometrial cancer.  Cancer. 1989;  64 1011-1016
• 71 Volker P, Grundker C, Schmidt O, Schulz K D, Emons G. Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: frequency, autoregulation, and correlation with direct antiproliferative activity hormone releasing hormone analogues.  Am J Obstet Gynecol. 2002;  186 171-179
• 72 Wang C-B, Wang C-J, Huang H-J, Hsueh S, Chou H-H, Soong Y-K, Lai C-H. Fertility-Preserving treatment in young patients with endometrial adenocarcinoma.  Cancer. 2002;  94 2192-2198
• 73 Yura Y, Tauchi K, Koshiyama M, Konishi J, Yura S, Mori T, Matasushita K, Hayashi M, Yoshida M. Parametrial involvement in endometrial carcinomas: its incidence and correlation with other histological parameters.  Gynecol Oncol. 1996;  63 114-119
• 74 Zaino R J. III. Endometrial hyperplasia: is it time for a quantum leap to a new classification?.  Int J Gynecol Pathol. 2000;  19 314-321
• 75 Zaino R J, Hershey M S. The fruits of our labours: distinguishing endometrial from endocervical adenocarcinoma.  Int J Gynecol Pathol. 2002;  21 1-3
• 76 Zanetta G, Gabriele A, Losa G, Capellini A, Mangioni C. Conservative management of endometrial carcinoma with prolonged preservation of the uterus in a young patient.  Int J Gynecol Cancer. 1997;  7 332-334
• 77 Zanotti K M, Belinson J L, Kennedy A W, Webster K D, Marckman M. The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma.  Gynecol Oncol. 1999;  74 272-277

1 Auszugsweise vorgetragen am 23. 02. 2002 anlässlich „Gynäkologie und Geburtshilfe, Frankfurt, 2002”