IMMUNOHISTOCHEMICAL EXPRESSION OF BCL-2 ONCOPROTEIN IN EBV-ASSOCIATEDNASOPHARYNGEAL CARCINOMA CORRELATED TO HISTOLOGICAL TYPE AND SURVIVAL

Expression of Bcl-2 is associated with inhibition of apoptosis and ext ension of cell survival. In vitro Bcl-2 protein expression is up-regul ated by the EBV-latency associated antigen latent membrane protein (LM P-1). We have investigated the relationship between the presence of EB V-DNA screened by means of sensitive nested-PCR, nasopharyngeal carcin oma (NPC) histological types according to two different schemata (WHO and Micheau classifications) and Bcl-2-124 immunohistochemical express ion in 55 biopsy samples of NPC. EBV genome was detected in 100% of sa mples with sufficient DNA quality to support the previous view that al l types of NPC are variants of EBV-infected neoplasia. Bcl-2 was obser ved in the basal layer of normal nasopharyngeal mucosa and also at cyt oplasmic 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 a ssociated (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 lo cation, clinical stage and age or sex of the patients in relation to B cl-2 positive expression. However, when comparing Bcl-2 expression and known survival mean of the patients, significant differences were obs erved (p<0.001) so that mean survivals were 31.1, 24.4, 52.2 and 54.1 months respectively for NPC patients with -, +, ++ and +++ Bcl-2 immun oreactivity. Nevertheless this better clinical outcome in Bcl-2 NPC po sitive cases may depend on the histological type due to close relation ship 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.