Cyclooxygenase-2, angiogenesis, tumor cell proliferation, P-glycoprotein in advanced ovarian serous carcinoma

Abstract

To the Editors: We read with great interest the study by Ali-Fehmi et al1Ali-Fehmi R. Morris R.T. Bandyopadhyay S. Che M. Schimp V. Malone Jr., J.M. et al.Expression of cyclooxygenase-2 in advanced stage ovarian serous carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, and survival.Am J Obstet Gynecol. 2005; 192: 819-825Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar regarding the role of cyclo-oxygenase-2 (COX-2) and angiogenesis in ovarian carcinoma. In a previous analysis, we investigated the COX-2 status in relation to tumor microvessel density (MVD) analyzed with the anti-CD34 monoclonal antibody, and vascular endothelial growth factor (VEGF) expression in a series of homogeneous untreated advanced serous ovarian carcinoma patients with low and high survival rate.2Raspollini M.R. Amunni G. Villanucci A. Boddi V. Baroni G. Taddei A. et al.COX-2 status in relation to tumor microvessel density (MVD) and VEGF expression. Analysis in ovarian carcinoma patients with low and high survival.Oncol Rep. 2004; 11: 309-313PubMed Google Scholar In the above-mentioned study, MVD ≥70 microvessels for 200× microscopic fields was correlated with COX-2 (P = .009) and with VEGF expression (P = .003), and also, COX-2 and VEGF were correlated with one another (P = .044), according to Fisher exact test. In addition, the evaluation of COX-2 status, MVD, and VEGF expression in relation to low and high survival according to the logistic regression analysis was statistically significant (P = .017, P = .008, P < .0005, respectively). We first hypothesized that molecular-targeted therapies for ovarian carcinoma as angiogenesis inhibitors or COX-inhibitors may possibly have synergistic effects with chemotherapy in the ovarian cancer patients with COX-2 and VEGF expression and high MVD. In addition, in a subsequent report,3Raspollini M.R. Amunni G. Villanucci A. Boddi V. Taddei G.L. Increased cyclooxygenase-2 (COX-2) and P-glycoprotein-170 (MDR1) expression are associated with chemotherapy resistance and poor prognosis. Analysis in ovarian carcinoma patients with low and high survival.Int J Gynecol Cancer. 2005; 15: 255-260Crossref PubMed Scopus (45) Google Scholar we observed that P-glycoprotein is correlated with COX-2 (P = .008, Fisher exact test); moreover, both COX-2 and the P-glycoprotein were correlated with clinical response to chemotherapy (P = .022 and P < .0005, respectively, chi-square test). The COX-2 and the P-glycoprotein expressions are correlated with one another and both with a progression of disease during the first line chemotherapy. The administration of a COX-2 inhibitor in association with chemotherapy in ovarian carcinoma patients may improve the tumor chemosensitivity and the overall survival. In addition, in a previous study in advanced serous ovarian cancer patients4Raspollini M.R. Amunni G. Villanucci A. Baroni G. Boddi V. Taddei G.L. Prognostic value of P-glycoprotein and proliferative index in advanced low grade serous ovarian carcinomas.J Chemoth. 2003; 15: 359-365Google Scholar we observed both that P-glycoprotein (P = .001 and P < .0005) and proliferative index (P = .081 and P = .041) were independent predictors of brief disease-free interval and survival (multivariate analysis), and that P-glycoprotein (P < .0005) and proliferative index (P = .008) were associated with clinical response to chemotherapy. The data shown by Ali-Fermi's study give additional experimental evidence to our findings, and both suggest the study of molecolar markers, which may allow the selection of some patients as candidates for more tailored therapies. ReplyAmerican Journal of Obstetrics & GynecologyVol. 194Issue 4PreviewWe would like to thank Dr Raspollini et al for their comments. We are excited to see that many groups have found similar results with respect to overexpression of COX-2 in epithelial ovarian cancer and the association of those changes with various markers of progression. COX-2 overexpression and its negative impact on patients' prognosis have been described in many malignancies from various primary sites. It has been shown that this protein may contribute to tumor progression through a number of pathways, including the induction of angiogenesis. Full-Text PDF