Bcl‐2 proto‐oncogene expression in epstein‐barr‐virus‐associated nasopharyngeal carcinoma

Abstract

The bcl‐2 proto‐oncogene product inhibits apoptosis. Increased levels of bcl‐2 protein are associated with prolonged B‐cell survival and have been demonstrated in a high proportion of follicular B‐cell lymphoma. Recent studies have shown that bcl‐2 protein expression in B cells immortalized by Epstein‐Barr virus (EBV) in vitro is up‐regulated by the EBV‐latency‐associated antigen, latent membrane protein (LMP) I. The epithelial malignancy, undifferentiated nasopharyngeal carcinoma (UNPC), has a well‐established association with EBV and the tumour cells characteristically display a restricted latent viral phenotype including LMP I. This study has investigated the relationship between the presence of EBV DNA, EBV phenotypic profiles and bcl‐2 protein expression in conventionally processed and cryopreserved samples of NPC using in situ hybridization, immunocytochemical and immunoblotting techniques. bcl‐2 was detected in most (80%) samples of UNPC as well as in 1/3 samples of keratinizing NPC and 2/2 samples of nasopharyngeal adenocarcinoma. However, no close correlation was found between the presence of EBV DNA, and profiles for LMP I and bcl‐2 protein expression in 45 UNPC. In addition, bcl‐2 protein was shown to be selectively expressed in the basal compartment of normal nasopharyngeal epithelia. bcl‐2 protein expression has not been reported previously in malignant tumours of epithelial origin. The findings in this study implicate a role for bcl‐2 both in normal keratinocyte differentiation and in the pathogenesis of epithelial malignancy.