Prognostic Significance of COX-2 Expression and Correlation With Bcl-2 and VEGF Expression, Microvessel Density, and Clinical Variables in Classical Hodgkin Lymphoma

Abstract

Vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) play important roles in tumor angiogenesis. Recent reports found that COX-2 expression had prognostic value in classical Hodgkin lymphoma (cHL). The purpose of this study was to measure the expression of COX-2, B-cell lymphoma-2 (Bcl-2), VEGF, and CD31 and assess their prognostic significance and potential correlation with clinical variables in cHL. A total of 167 cHL specimens were evaluated retrospectively by immunohistochemical methods for COX-2, Bcl-2, and VEGF expression and for CD31 to measure the microvessel density (MVD). Correlations between COX-2, Bcl-2, VEGF, MVD, and clinicopathologic factors were assessed, and prognostic significance was determined. COX-2, Bcl-2, and VEGF were expressed in 27.5%, 8.3%, and 33.5% of the specimens, respectively. A positive correlation was found between COX-2 and VEGF expression (P<0.001). The MVD was significantly higher in tumors positive for both COX-2 and VEGF compared with that in tumors negative for both markers (P=0.047). COX-2 expression was associated with a lower overall survival rate (P=0.015). High MVD was associated with a lower event-free survival rate (P=0.014). COX-2 was an independent prognostic factor for overall survival on multivariate analysis (P=0.013). COX-2 and VEGF correlated with angiogenesis and tumor progression in cHL. The findings support targeting COX-2 as a potential new therapeutic approach in cHL.