COX-2-Expression in extragenitalen Endometrioseläsionen als neuer Therapieansatz?

Zusammenfassung

Fragestellung: Die extragenitale Endometriose ist eine seltene Sonderform der Endometriose, bei der durch das invasive, metastatische Wachstum das tumorähnliche Verhalten der Erkrankung besonders deutlich wird. Cyclooxygenase (COX)-2 ist ein Schrittmacherenzym der Prostaglandinsynthese, das insbesondere bei inflammatorischen und malignen Prozessen exprimiert wird. In dieser Studie sollte untersucht werden, ob in extragenitaler Endometriose COX-2 exprimiert wird.
Material und Methoden: Von 13 Frauen mit extragenitaler Endometriose wurden Gewebeproben von rektaler und vaginaler Endometriose, Narbenendometriose und Endometriose des Omentum majus gewonnen. Die COX-2-Expression wurde immunohistochemisch untersucht.
Ergebnisse: Es zeigte sich eine Ü berexpression in glandulärem Drüsenepithel in allen Gewebeproben und eine schwache bis mittlere Expression in der Hälfte der untersuchten Proben. Zum Zeitpunkt der Operation durchgeführte Hormontherapien hatten keinen Einfluss auf die COX-2-Expression.
Schlussfolgerung: Die hohe COX-2-Expression in der extragenitalen Endometriose korreliert möglicherweise mit der Pathogenese der Endometriose.

Abstract

Objective: Extragenital endometriosis is a rare form of endometriosis. Due to its invasive and metastatic properties it resembles some features of malignant tumours. Cyclooxygenase (COX)-2 is a rate-limiting enzyme in the biosynthesis of prostaglandins and is mainly expressed in inflammatory and malignant processes. In this study we investigated the COX-2 expression in extragenital endometriosis.
Material and Methods: Tissue was obtained of 13 women with rectal and vaginal endometriosis, scar endometriosis and endometriosis of the omentum majus. The COX-2 expression was investigated by immunohistochemistry.
Results: In the glandular epithelium a COX-2 overexpression was found in all cases and in the stroma a weak to moderate COX-2 expression was found in half of the cases. A hormonal therapy at the time of surgery had no influence on the COX-2 expression in extragenital endometriosis.
Conclusion: The high COX-2 expression in extragenital endometriosis is believed to be strongly correlated with the pathological abnormalities this of disease.

Schlüsselwörter

Endometriose - extragenital - Cyclooxygenase - COX-2 - Prostaglandine - Therapie

Key words

Endometriosis - extragenital - cyclooxygenase - COX-2 - prostaglandins - therapy

Literatur

• 1 Attia G R, Zeitoun K, Edwards D, Johns A, Carr B R, Bulun S E. Progesterone receptor isoform A but not B is expressed in endometriosis.  J Clin Endocrinol Metab. 2000;  85 2897-2902
• 2 Berqvist A. Extragenital Endometriosis.  Eur J Surg. 1992;  158 7-12
• 3 Berqvist A. Different types of extragenital endometriosis: a review.  Gynecol Endocrinol. 1993;  7 207-221
• 4 Bulun S E, Zeitoun K M, Takayama K, Sasano H. Molecular basis for treating endometriosis with aromatase inhibitors.  Hum Reprod Update. 2000;  6 413-418
• 5 Chishima F, Hayakawa S, Sugita K, Kinukawa N, Aleemuzzaman S, Nemoto N, Yamamoto T, Honda M. Increased expression of cyclooxygenase-2 in local lesions of endometriosis patients.  Am J Reprod Immunol. 2002;  48 50-56
• 6 Cornillei F J, Oosterlynck D, Lauweryns J M, Koninckx P R. Deeply infiltrating pelvic endometriosis: Histology and clinical significance.  Fertil Steril. 1990;  53 978-983
• 7 Davies G, Martin L A, Sacks N, Dowsett M. Cyclooxygenase-2 (COX-2), aromatase and breast cancer: a possible role for COX-2 inhibitors in breast cancer chemoprevention.  Ann Oncol. 2002;  13 669-678
• 8 Dawood M Y. Peritoneal fluid prostaglandins and prostaniods in women with endometriosis, chronic pelvic inflammatory disease, and pelvic pain.  Am J Obstet Gynecol. 1984;  173 125-134
• 9 Denkert C, Köbel M, Pest S, Koch I, Berger S, Schwabe M, Siegert A, Reles A, Klosterhalfen B, Hauptmann S. Expression of cyclooxygenase 2 is an independent prognostic factor in human ovarian carcinoma.  Am J Pathol. 2002;  160 893-903
• 10 Dormond O, Foletti A, Paroz C, Ruegge C. NSAIDs inhibit αVβ3 integrin mediated and Cdc42/Rac dependent endothelial-cell spreading, migration and angiogenesis.  Nature Med. 2001;  7 1041-1047
• 11 DuBois R N, Abramson S B, Crafford L, Gupta R A, Simon L S, VanDePutte L B, Lipsky P E. Cyclooxygenase in biology and desease.  FSAEB J. 1998;  12 1063-1073
• 12 Ferrandina G, Legge F, Ranelleti F O, Zannoni G F, Maggiano N, Evangelisti A, Manusco S, Scambia G, Lauriola L. Cyclooxygenase-2 expression in endometrial carcinoma, correlation with clinicopthologic parameters and clinical outcome.  Cancer. 2002;  95 801-807
• 13 Form D M, Auerbach R. PGE2 and angiogenesis.  Proc Soc Exp Biol Med. 1983;  172 214-218
• 14 Gaetje R, Kotzian S, Herrmann G, Baumann R, Starzinsky-Powitz A. Invasiveness of endometriotic cells in vitro.  Lancet. 1995;  150 1463-1464
• 15 Gebel H M, Braun D P, Tambur A, Frame D, Rana N, Dmowski W P. Spontaneus apoptosis of endometrios is impaired in women with endometriosis.  Fertil Steril. 1998;  69 1042-1047
• 16 Graeber J E, Glase B M, Setty B NY, Jerdan J A, Walega R W, Stuart M J. 15-Hydroxyeicosathtraenoic acid stimulates migration of human retinal microvessels.  Prostaglandins. 1990;  39 665-673
• 17 Half E, Tang X M, Gwyn K, Sahin A, Wathen K, Sinicrope F A. Cyclooxygenase-2 expression in human breast cancer and adjacent ductal carinoma in situ.  Cancer Res. 2002;  62 1676-1681
• 18 Hsu A L, Ching T T, Wang D S, Song X, Rangnekar V M, Chen C S. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Act activation in human prostate cancer cells independently of Blc-2.  J Biol Chem. 2000;  275 11397-11407
• 19 Jones R L, Kelly R W, Critchley H OD. Chemokine and cyclooxygenase-2 expression in human endometrium coincides with leukocyte accumulation.  Hum Reprod. 1997;  12 1300-1306
• 20 Lessey B A, Metzger D A, Haney A f, McCarthy K S. Immunohistochemical analysis of estrogen and progesterone receptors in endometriosis: comparison with normal endometrium during the menstrual cycle and the effect of medical therapy.  Fertil Steril. 1989;  51 409-415
• 21 Masferrer J L, Leahy K M, Koki A T, Zweifel B S, Stele S L, Woerner B M, Edwards D A, Flickinger A G, Moore R J, Seibert K. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors.  Cancer Res. 2000;  60 1306-1311
• 22 Muzii L, Riccardo M, Btunetti L, Orlando G, Michelotto B, Pancini P B. Atypical endometriosis revisited: clinical and biochemical evaluation of the different forms of superficial implants.  Fertil Steril. 2000;  74 736-742
• 23 Ota H, Igarashi S, Sasaki M, Tanaka T. Distribution of cyclooxygenase-2 in eutpic and ectopic endometrium in endometriosis and adenomyosis.  Hum Reprod. 2001;  16 561-566
• 24 Ryu H S, Chang K H, Yang H W, Kim M S, Kwan H C, Oh K S. High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion.  Gynecol Oncol. 2000;  76 320-325
• 25 Sheng H, Shao J, Morrow J D, Beauchamp R D, DuBois R N. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells.  Cancer Res. 1998;  58 362-366
• 26 Subbarabaiah K, Telang T, Ramonetti J T, Araki R, DeVito B, Weksler B B, Dannenberg A J. Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cell.  Cancer Res. 1996;  56 4424-4429
• 27 Ueki M. Histologic study of endometriosis and examination of lymphatic draining in and from the uterus.  Am J Obstet Gynecol. 1991;  165 201-209
• 28 Vernon M W, Beard J, Granve K, Wilson E A. Classification of endometriotic implants by morphologic appearance and capacity to synthesize prostaglandin F.  Fertil Steril. 1986;  46 801-806
• 29 Zhang L, Yu J, Park B H, Kinlzler K W, Vogelstein B. Role of BAX in the apoptotic response to anticancer agents.  Science. 2000;  290 982-989