title: Immunohistochemical 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 all types of NPC are variants of EBV-infected neoplasia. Bcl-2 was observed in the basal 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 31.1, 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.
authors.affiliation: Service of Pathology II, Laboratory of Molecular Pathology, Hospital La Fe, Medical School of Valencia University, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Vera-Sempere
authors.forename: J S
authors.initials: JS
authors.lastname: Burgos
authors.forename: M S
authors.initials: MS
authors.lastname: Botella
authors.forename: C
authors.initials: C
authors.lastname: Morera
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D019253:Proto-Oncogene Proteins c-bcl-2