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AIM:To clarify the significance of JC virus(JCV)T-antigen (T-Ag)expression in human gastric cancer. METHODS:We investigated the relationship between T-Ag detected by immunohistochemistry and Epstein- Barr virus(EBV)infection,microsatellite instability (MSI),and genetic and epigenetic alterations in gastric cancers.Mutations in the p53,β-catenin,KRAS,BRAF, PIK3CA genes were analyzed by polymerase chain reaction(PCR)-single strand conformation polymorphism and DNA sequencing.Allelic losses were determined by PCR at 7 microsatellite loci.Aberrant DNA methylation was analyzed by MethyLight assay. RESULTS:JCV T-Ag protein expression was found in 49%of 90 gastric cancer tissues.T-Ag positivity was not correlated with clinicopathological characteristics. T-Ag expression was detected in a similar percentage of EBV positive cancers(4 of 9,44%)and EBV negativecancers(35 of 73,48%).T-Ag expression was detected in a significantly lower percentage of MSI-H cancers (14%)than in non MSI-H cancers(55%,P=0.005). T-Ag expression was detected in a significantly higher percentage of cancers with nuclear/cytoplasmic localization of catenin(15 of 21,71%)than in cancers without(42%,P=0.018).p53 mutations were detected in a significantly lower percentage of T-Ag positive cancers(32%)than in T-Ag negative cancers(57%,P= 0.018).T-Ag positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation compared with T-Ag negative gastric cancers(P=0.008 and P=0.003). CONCLUSION:The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.
METHODS: We investigated the relationship between T-Ag detected by immunohistochemistry and Epstein-Barr virus (EBV) infection, microsatellite instability (MSI), and genetic and epigenetic alterations in gastric cancers. Mutations in the p53, β-catenin, KRAS, BRAF, PIK3CA genes were analyzed by polymerase chain reaction (PCR) -single strand conformation polymorphism and DNA sequencing. Allelic losses were determined by PCR at 7 microsatellite loci. Aberrant DNA methylation was analyzed by MethyLight assay. RESULTS: JCV T-Ag protein expression was found in 49% of 90 gastric cancer tissues. T-Ag positivity was not correlated with clinicopathological characteristics. T-Ag T-Ag expression was detected in a similar percentage of EBV positive cancers (4 of 9, 44%) and EBV negativecancers (35 of 73, 48%). T-Ag expression was detected in a significantly lower percentage of MSI- than in non MSI-H cancers (55 %, P = 0.005). T-Ag expression was detected in a significantly higher percentage of cancers with nuclear / cytoplasmic localization of catenin (15 of 21,71%) than in cancers without (42%, P = T-Ag positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation (57%, P = 0.018) were detected in a significantly lower percentage of T-Ag positive cancers (32% compared with T-Ag negative gastric cancers (P = 0.008 and P = 0.003) CONCLUSION: The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.