Epstein-Barr virus positivity is associated with angiogenesis in, and poorer survival of, patients receiving standard treatment for classical Hodgkin's lymphoma

Abstract

Epstein-Barr virus (EBV) is a significant contributor to the development of classical Hodgkin's lymphoma (cHL). Recent studies have documented associations between angiogenesis and EBV-associated malignancies. No study has yet examined the associations among, and prognostic implications of, EBV infection, vascular endothelial growth factor (VEGF) expression, and microvessel density (MVD) in cHL patients. Diagnostic tissues from 135 cHL patients treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) were retrospectively evaluated by in situ hybridization of EBV-encoded small RNA (EBER) and immunohistochemical staining for VEGF and CD31 (a measure of MVD). EBER and VEGF expression were positively correlated (P = 0.038). The mean MVD value of EBER-positive tumors was significantly higher than that of EBER-negative tumors (P = 0.034). The mean MVD of tumors positive for both EBER and VEGF was significantly higher than that of tumors negative for both markers (P = 0.008). EBER-positive patients had a lower 5-year overall survival (OS) rate than EBER-negative patients (P = 0.046). A high MVD was also associated with a poorer OS (P = 0.01); multivariate analysis showed that this was a significant and independent prognostic factor (P = 0.026). We found positive correlations between EBER and VEGF levels, and the MVD, indicating that EBV plays an important role in tumor angiogenesis. Targeting of both angiogenesis and EBV may be important when treating cHL patients who are EBER-positive and/or have a high MVD.

Keywords: EBV; Hodgkin's lymphoma; VEGF; microvessel density; prognosis.