lmmunohistochemical expression of Bcl-2 oncoprotein in EBV-associated nasopharyngeal carcinoma correlated to histological type and survival

Abstract

Expression of Bcl-2 is associated with inhibition of apoptosis and extension of cell survival. In vitro Bcl-2 protein expression is up-regulated by the EBV-latency associated antigen latent membrane protein (LMP-1). We have investigated the relationship between the presence of EBV-DNA screened by means of sensitive nested-PCR, nasopharyngeal carcinoma (NPC) histological types according to two different schemata (WHO and Micheau classifications) and Bcl-2-124 immunohistochemical expression in 55 biopsy samples of NPC. EBV genome was detected in 100% of samples with sufficient DNA quality to support the previous view that al1 types of NPC are variants of EBV-infected neoplasia. Bcl-2 was observed in the basa1 layer of normal nasopharyngeal mucosa and also at cytoplasmic level in 42 of 55 (76.4%) NPC cases. Mitotic neoplastic cells usually showed strong cytoplasmic and chromosomal staining, a finding not well referred to previously. Bcl-2 expression was significantly associated (p<0.05) to undifferentiated NPC (UNPC) when a histological classification with only two major microscopical types was applied. No close correlations were found between the presence of EBV-DNA, NPC location, clinical stage and age or sex of the patients in relation to Bcl-2 positive expression. However, when comparing Bcl-2 expression and known survival mean of the patients, significant differences were observed (p<0.001) so that mean survivals were 3 1.1, 24.4, 52.2 and 54.1 months respectively for NPC patients with -, +, ++ and +++ Bcl-2 immunoreactivity. Nevertheless this better clinical outcome in Bcl-2 NPC positive cases may depend on the histological type due to close relationship with UNPC. Only studies of larger series with long-term follow-up and multivariate analyses may document whether Bcl-2 expression is an independent prognostic marker in the evolution of NPC patients.