Extracellular matrix metalloproteinase inducer (EMMPRIN) expression correlates positively with active angiogenesis and negatively with basic fibroblast growth factor expression in epithelial ovarian cancer

Sebastian Szubert,Slawomir Michalak,Stefan Sajdak,Andrzej Frankowski,Rafal Moszynski,Michal Nowicki,Dariusz Szpurek

doi:10.1007/s00432-013-1569-z

Abstract

PurposeThe primary aim of this paper was to evaluate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its relationship with proangiogenic factors and microvessel density (MVD) in ovarian cancer.MethodsThe study group included 58 epithelial ovarian cancers (EOCs), 35 benign ovarian tumors, and 21 normal ovaries. The expression of EMMPRIN, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) was assessed by ELISA of tissue homogenates. Antibodies against CD105, CD31, and CD34 were used to immunohistochemically assess MVD.ResultsWe have found significantly higher EMMPRIN expression in EOC than in benign ovarian tumors and normal ovaries. Similarly, the VEGF expression was higher in EOC than in benign ovarian tumors and normal ovaries. By contrast, bFGF expression was lower in EOC than in benign ovarian tumors and ovary samples. EMMPRIN expression in EOC was directly correlated with VEGF expression and CD105-MVD, but inversely correlated with bFGF expression. Grade 2/3 ovarian cancers had increased expression of EMMPRIN and VEGF, increased CD105-MVD, and lowered expression of bFGF compared to grade 1 ovarian cancers. Moreover, EMMPRIN expression was higher in advanced (FIGO III and IV) ovarian cancer.ConclusionsThe upregulation of EMMPRIN and VEGF expression is correlated with increased CD105-MVD and silenced bFGF, which suggests early and/or reactivated angiogenesis in ovarian cancer. Aggressive EOC is characterized by the following: high expression of EMMPRIN and VEGF, high CD105-MVD, and low expression of bFGF.

Highlights

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancies and the fifth leading cause of cancer-related death among women in the United States (Jemal et al 2010)
The median basic fibroblast growth factor (bFGF) expression was significantly lower in the EOC group compared to the benign ovarian tumor and normal ovary groups (P < 0.0001)
The results of our study indicate that extracellular matrix metalloproteinase inducer (EMMPRIN) may contribute to the development of new blood vessels in ovarian cancer

Summary

Introduction

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancies and the fifth leading cause of cancer-related death among women in the United States (Jemal et al 2010). Two randomized placebo-controlled trials reported a significant response and prolonged progressionfree survival (PFS) after the incorporation of bevacizumab, an anti-VEGF monoclonal antibody, into the primary chemotherapy regimen for ovarian cancer patients (Burger et al 2011; Perren et al 2011). In the case of recurrent or persistent ovarian cancer, bevacizumab monotherapy produced a 16–21 % response rate, and the median PFS was less than 5 months (Burger et al 2007; Cannistra et al 2007) Taken together, these results suggest that anti-VEGF therapy in ovarian cancer is effective but insufficient. Potential strategies include the application of multikinase inhibitors that impede the signaling of several important proangiogenic molecules, such as VEGF, platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) Such multikinase inhibitors are currently in clinical trials in ovarian cancer patients (Burger 2011)

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