Immunohistochemical expression of MMP-2, MMP-9 and COX-2 in Stage IA malignant polyps of the endometrium

Objective: To study whether endometrioid type malignant endometrial polyps (MEP) are different from endometrium cancer not associated with polyps (ECNAP) in means of immunohistochemical expressions of MMP-2. MMP-9 and COX-2. Methods: Archived tissue samples of eight MER eight ECNAP and 16 benign endometrial polyps were selected and immunohistochemically analyzed for MMP-2, MMP-9 and COX-2 expression. Results: MMP-2 and MMP-9 were overexpressed in ECNAP compared to MEP and benign endometrial polyps (p < 0.05). MMP-2 and MMP-9 expressions were not different in the malignant part of MEP, benign part of MEP and benign endometrial polyps. COX-2 expression was found to be higher in benign lesions, although this was not statistically significant. Conclusion: Similar immunohistochemical expression of MMP-2. MMP-9 and COX-2 within a polyp and with benign polyps may indicate an immunohistochemically indolent characteristic of MEP.

Endometrial polyp; Endometrium cancer; Cyclooxygenase 2; Matrix metalloproteinase 2

[1] Prat J., Gallardo A., Cuatrecasas M., Catasus L.: “Endometrial carcinoma: pathology and genetics”. Pathology, 2007, 39, 72.

[2] Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 17 Regs Limited-Use, Nov 2006 Sub (1973-2004 varying), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2007, based on the November 2006 submission.

[3] Prat J.: “Prognostic parameters of endometrial carcinoma”. Hum. Pathol., 2004, 35, 649.

[4] Woessner J.F Jr.: “Matrix metalloproteinases and their inhibitors in connective tissue remodeling”. FASEB J., 1991, 5, 2145.

[5] Giannelli G., Falk-Marzillier J., Schiraldi O., Stetler-Stevenson W.G., Quaranta V.: “Induction of cell migration by matrix metalloproteinase- 2 cleavage of laminin-5”. Science, 1997, 277, 225.

[6] Iurlaro M., Loverro G., Vacca A., Cormio G., Ribatti D., Minischetti M. et al.: “Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 correlate with upgrading and myometrial invasion in endometrial carcinoma”. Eur. J. Clin. Invest., 1999, 29, 793.

[7] Graesslin O., Cortez A., Uzan C., Birembaut P., Quereux C., Daraï E.: “Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions”. Int. J. Gynecol. Cancer, 2006, 16, 1911.

[8] Di Nezza L.A., Misajon A., Zhang J., Jobling T., Quinn M.A., Ostör A.G. et al.: “Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion”. Cancer, 2002, 94, 1466.

[9] Chandrasekharan N.V., Simmons D.L.: “The cyclooxygenases”. Genome Biol., 2004, 5, 241.

[10] Cao Y., Prescott S.M.: “Many actions of cyclooxygenase-2 in cellular dynamics and in cancer”. J. Cell. Physiol., 2002, 190, 279.

[11] Vane J.: “Towards a better aspirin”. Nature, 1994, 367, 215.

[12] Voutsadakis I.A.: “Pathogenesis of colorectal carcinoma and therapeutic implications: the roles of the ubiquitin-proteasome system and Cox-2”. J. Cell. Mol. Med., 2007, 11, 252.

[13] Erkanli S., Bolat F., Kayaselcuk F., Demirhan B., Kuscu E.: “COX-2 and surviving are overexpressed and positively correlated in endometrial carcinoma”. Gynecol. Oncol., 2007, 104, 320.

[14] Genc S., Attar E., Gurdol F., Kendigelen S., Bilir A., Serdaroglu H.: “The effect of COX-2 inhibitor, nimesulide, on angiogenetic factors in primary endometrial carcinoma cell culture”. Clin. Exp. Med., 2007, 7, 6.

[15] Anastasiadis P.G., Koutlaki N.G., Skaphida P.G., Galazios G.C., Tsikouras P.N., Liberis V.A.: “Endometrial polyps: prevalence, detection, and malignant potential in women with abnormal uterine bleeding”. Eur. J. Gynaecol. Oncol., 2000, 21, 180.

[16] Antunes A. Jr., Costa-Paiva L., Arthuso M., Costa J.V., Pinto-Neto A.M.: “Endometrial polyps in pre- and postmenopausal women: Factors associated with malignancy”. Maturitas, 2007, 20, 57, 415.

[17] Farrell R., Scurry J., Otton G., Hacker N.F.: “Clinicopathologic review of malignant polyps in stage 1A carcinoma of the endometrium”. Gynecol. Oncol., 2005, 98, 254.

[18] Coeman D., Van Belle Y., Vanderick G., De Muylder X., De Muylder E., Campo R.: “Hysteroscopic findings in patients with a cervical polyp”. Am. J. Obstet. Gynecol., 1993, 169, 1563.

[19] Remmele W., Stegner H.E.: “Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue”. Pathologe, 1987, 8, 138.

[20] Ohno Y., Ohno S., Suzuki N., Kamei T., Inagawa H., Soma G. et al.: “Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma”. Int. J. Cancer, 2005, 114, 696.

[21] Kase S., Osaki M., Honjo S., Adachi H., Tsujitani S., Kaibara N. et al.: “Expression of cyclo-oxygenase-2 is correlated with high intratumoral microvessel density and low apoptotic index in human esophageal squamous cell carcinomas”. Virchows Arch., 2003, 442, 129.

[22] Tsujii M., Kawano S., DuBois R.N.: “Cyclooxygenase-2 expression in Human colon cancer cells increases metastatic potential”. Proc. Natl. Acad. Sci U S A, 1997, 94, 3336.

[23] Orejuela F.J., Ramondetta L.M., Smith J., Brown J., Lemos L.B., Li Y. et al.: “Estrogen and progesterone receptors and cyclooxygenase-2 expression in endometrial cancer, endometrial hyperplasia, and normal endometrium”. Gynecol. Oncol., 2005, 97, 483.

[24] Nasir A., Boulware D., Kaiser H.E., Lancaster J.M., Coppola D., Smith P.V. et al.: “Cyclooxygenase-2 (COX-2) expression in human endometrial carcinoma and precursor lesions and its possible use in cancer chemoprevention and therapy”. In Vivo, 2007, 21, 35.

[25] Aglund K., Rauvala M., Puistola U., Angstrom T., Turpeenniemi- Hujanen T., Zackrisson B. et al.: “Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage”. Gynecol. Oncol., 2004, 94, 699.

[26] Carcangiu M.L., Tan L.K., Chambers J.T.: “Stage 1A uterine serous carcinoma: a study of 13 cases”. Am. J. Surg. Pathol., 1997, 21, 1507.