The aim of this study was to detect the expression of proliferatng cell nuclear antigen (PCNA) and c-myc in Epstein‑Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), as well as the expression of EBV-encoded proteins in EBVaGC and their effect on carcinogenesis and the development of gastric cancer. The PCNA and c-myc protein levels were assessed by immunohistochemistry in 13 EBVaGC and 45 EBVnGC specimens. The expression of related genes of EBV, including EB nuclear antigen (NA)-1 and EBNA2 genes, latent membrane protein 1 (LMP1) and early genes BARF1 and BHRF1 were tested by reverse transcription-polymerase chain reaction (RT-PCR) and southern blotting. The PCNA labeling index (LI) of EBVaGCs, EBVnGCs and the corresponding adjacent tissues of EBVaGCs were 49.3768±12.1832, 14.839±7.1847, 35.613±8.3831 and 24.2735±10.1332, respectively. The PCNA LI was significantly different between EBVaGC and EBVnGC of EBVaGC (t=4.686, P<0.01). The difference between EBVaGC and corresponding adjacent tissues of EBVaGC was also significant (t=8.805, P<0.01). The expression of c-myc protein was detected in 33 of 58 (55.39%) gastric carcinomas and in 21 of 58 (36.21%) adjacent tissues. There was a significant difference between the two groups (χ2=4.989, P0.05). EBNA1 mRNA was detected in all 13 EBVaGC cases, while EBNA2 and LMP1 mRNA was not detected in these cases. Of the 13 EBV-positive samples, 6 exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts. c-myc expression did not correlate with the presence of EBV in EBVaGC. EBV infection may induce PCNA expression. The lack of EBNA2 and LMP1 protein expression in EBVaGC suggests that EBNA2 and LMP1 do not correlate with cell apoptosis and c-myc expression. Early genes BARF1 and BHRF1 may play an important role in the development and progression of gastric carcinomas by immortalizing epithelial cells.

Correlation of Epstein-Barr virus and its encoded proteins with Helicobacter pylori and expression of c-met and c-myc in gastric carcinoma

Objectives: To characterize the specific Epstein-Barr virus (EBV) polymorphisms from nasopharyngeal carcinoma (NPC) patients and healthy donors in Northern China, and to explore the relationship between the EBV genotypes and NPC. Methods: The genotypes of EBV strains were analyzed by the polymerase chain reaction and restriction fragment length polymorphism. Results: The predominant EBV type was A, C or F in both NPC and healthy individuals. The distributions of the EBV subtypes between NPC and healthy donors were not significantly different (p > 0.05). The frequency of type f strains in NPC was significantly lower in Northern China than in Southern China. Conclusions: No evidence of special EBV genotypes associated with NPC was found, suggesting that EBV strains derived from the NPC patients may reflect geographic distribution rather than being NPC restricted.

Background. Retinoblastoma (RB) and transforming growth factor-β1 (TGF-β1) are important tumor-related factors.Methods. A series of 30 EBV-associated gastric carcinoma (EBVaGC) and 38 matched EBV-negative gastric carcinoma (EBVnGC) tissues were examined for the promoter methylation ofRBby methylation-specific PCR (MSP) method. The expression ofRBandTGF-β1in gastric carcinoma tissues was detected by immunohistochemistry.Results. The methylation rate ofRBgene in EBVaGC and EBVnGC was 80.0% (24/30) and 50.0% (19/38), respectively. The difference ofRBmethylation rate between EBVaGC and EBVnGC was significant(χ2=6.490, P=0.011). There was no significant difference forRBexpression between EBVaGC (43.3%, 13/30) and EBVnGC (63.2%, 24/38), and also forTGF-β1between EBVaGC (56.7%, 17/30) and EBVnGC (63.2%, 24/38).RBmethylation was not reversely correlated withRBexpression in gastric carcinoma tissues(χ2=2.943, P=0.086, r=0.208).RBmethylation, loss expression ofRB, andTGF-β1expression were significantly associated with tumor invasion and lymph node metastasis (P<0.05), but was not associated with sex, age, histological subtype (differentiation status) and tumor location.Conclusions. Methylation ofRBis a common event in gastric carcinomas and EBV induces methylation ofRBin EBVaGC, which may contribute to the development of gastric carcinomas. EBV has no significant effect on induction ofTGF-β1expression. Detection ofRBmethylation,RBexpression, andTGF-β1expression may be helpful to judge the status of tumor invasion and lymph node metastasis in gastric carcinomas.