title: Co-expression of p53 and bcl-2 may correlate to the presence of epstein-barr virus genome and the expression of proliferating cell nuclear antigen in nasopharyngeal carcinoma.
abstract: Epstein-Barr virus (EBV) has been well documented in the aetiology of nasopharyngeal carcinoma (NPC), although its role as well as the genetic basis in the genesis of NPC have not been elucidated. The p53 gene mutations are infrequently found in NPC, but the expression of p53 protein, as well as bcl-2 oncoprotein, has been reported in a high percentage of cases, and also in association with EBV. Proliferating cell nuclear antigen (PCNA) has also been shown to be increased in NPC, suggesting its association among the overexpression of p53 and bcl-2 oncoprotein. We undertook this study to evaluate the correlation among these abnormalities in the development of NPC. The expression of p53 protein, bcl-2 oncoprotein, and the level of PCNA were investigated by immunohistochemistry in 53 patients with NPC. Twenty tissue samples from these patients were studied for p53 gene mutations by single strand conformation polymorphism (SSCP) and DNA sequencing as well as EBV genomes by polymerase chain reaction. Among the 53 specimens, 42 (79%) showed expression of p53 protein and 40 (75%) gave positive result for bcl-2 oncoprotein. A significant association was found between p53 expression and bcl-2 oncoprotein (P=0.002; Fisher's exact test) with 68% of the patients showing coexpression of both markers. The PCNA labelling index in the 53 patients varied from 5% to 80%. High PCNA labelling index was frequently found in the patients with overexpression of p53 protein and bcl-2 oncoprotein. The PCNA index in patients with p53 expression was significant higher than in those without p53 expression (P=0.002). Of the 20 patients, p53 mutations were found in four cases. EBV genomes were detected in 14 cases of which 12 cases showed overexpression of both p53 and bcl-2 and one case with only p53 expression and one case with bcl-2 expression. EBV genomes were detected in two cases with p53 mutations. We conclude that EBV is the important etiologic factor in NPC which may be involved in p53 and bcl-2 overexpression. The mutant p53 protein is correlated to deregulation of PCNA. p53 mutations participate in a small proportion of the tumorigenesis.
authors.affiliation: Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Rajthevi, 10400, Bangkok, Thailand. rasnh@mahidol.ac.th
authors.forename: S
authors.initials: S
authors.lastname: Niemhom
authors.forename: S
authors.initials: S
authors.lastname: Kitazawa
authors.forename: S
authors.initials: S
authors.lastname: Murao
authors.forename: S
authors.initials: S
authors.lastname: Kunachak
authors.forename: S
authors.initials: S
authors.lastname: Maeda
mesh_terms: D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53