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Aims: To evaluate the clinicopathological value of cell cycle regulators, the Wnt pathway, the NF-betaB pathway and Epstein-Barr virus (EBV) and to assess their relationships in gastric carcinoma., Methods: We investigated cell cycle regulators (p53, p21, Rb), APC, beta-catenin and NF-kappaB using immunohistochemistry and EBV using in situ hybridisation for EBV encoded small RNAs in 117 cases of gastric carcinoma., Results: p53 overexpression was more frequently observed in advanced gastric carcinoma and lymph node metastasis than in early carcinoma or in the absence of metastasis (p < 0.05). p21 loss was positively correlated with APC loss, but inversely correlated with beta-catenin nuclear accumulation and NF-kappaB positivity (p < 0.05). EBV positive gastric carcinomas were located in the upper third of the stomach, and more were of the diffuse or mixed types than the EBV negative group (p < 0.05). EBV infection was positively correlated with p21 loss and APC loss and inversely correlated with beta-catenin alteration (p < 0.05). In multivariate analysis, patient age, TNM stage and p53 were independent prognostic factors for gastric carcinoma., Conclusions: p53 status is a prognostic marker for gastric carcinoma. p21, APC, beta-catenin and NF-kappaB may be functionally interrelated in gastric carcinogenesis. Loss of p21 and APC may be involved in the carcinogenesis of EBV positive gastric carcinomas.

Unlike gastric carcinoma, associations of the Epstein-Barr virus (EBV) with carcinomas of other sites in the gastrointestinal tract have not yet been clarified. To elucidate these associations, we investigated the presence of EBV in 142 cases of esophageal carcinoma, 107 cases of ampulla of Vater carcinoma, and 274 cases of colorectal carcinoma in Korean patients using EBV-encoded small RNAs (EBER)-in situ hybridization (ISH). In all cases, none of the tumor cells showed a positive signal, indicating that EBV is not generally related to the carcinogenesis of these cancers. Some EBV-positive tumor-infiltrating lymphocytes (TILs) were found in 8 of 142 cases (5.6%) of esophageal carcinoma, 8 of 107 cases (7.5%) of ampulla of Vater cancer, and 35 of 274 cases (12.8%) of colorectal carcinoma. For comparison, EBER-ISH was performed in consecutive gastric carcinomas; the EBER signal on tumor cells was observed in 17 of 306 cases (5.6%), and EBV-positive TILs were seen in 31 of the 289 cases (10.7%). There was no statistically significant difference in the frequencies of cases with EBV-positive TILs among the gastrointestinal tract cancers. We suggest that the reservoir lymphocytes carrying EBV, like other inflammatory cells, are able to reach anywhere, and that the chance for an epithelial cell to be exposed to EBV is similar at different sites of the gastrointestinal tract, regardless of its carcinogenic effect on the epithelial cell. HUM PATHOL 32:297-301., (Copyright 2001 by W.B. Saunders Company)

We evaluated the rate of Epstein-Barr virus (EBV) infection in gastric carcinomas of Korean patients and investigated the associations between EBV infection and clinicopathological characteristics, the survival rates of patients, and p53 overexpression. EBV-encoded small RNA (EBER)-in situ hybridization and immunohistochemistry for p53 protein were done in 306 consecutive gastric carcinoma cases, of which 17 (5.6%) showed EBV infection. Of these 17 EBV-positive cases, one case strongly expressed p53 protein, while 98 (34%) of 285 EBV-negative cases overexpressed p53 (p < 0.05). The EBV-positive gastric carcinomas tended to have lymphoid stroma. They were mostly of the poorly differentiated type, negative for p53 immunoexpression, more prevalent in male patients, and diffuse according to Lauren's classification (p < 0.05). There was no significant difference in the survival rate for the EBV status. In conclusion, the EBV infection rate among gastric carcinomas in Korea is similar to that ascertained in other countries. An inverse correlation between EBV and p53 overexpression was disclosed. Further study is needed to find out whether or not two genetic changes could be functionally overlapping during gastric carcinogenesis.