LMP2A Research Articles

Clinicopathologic features and protein expression study of Epstein-Barr virus-associated gastric carcinoma in Guangzhou

To investigate the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas in Guangzhou, their clinicopathologic features and related protein expressions including DNMT1, p16, and cyclin D1. A total of 676 cases of EBV-associated gastric carcinoma were included in the study. The presence of EBV-encoded small RNA1 (EBER1), a marker for EBV infection, was analyzed by in-situ hybridization using formalin-fixed and paraffin-embedded tumor samples. Expression of EBV-encoded proteins, DNMT1, p16 and cyclin D1 were detected by immunohistochemistry. Forty-five of 676 gastric carcinomas showed EBER intranuclear positivity in all tumor cells. EBV involvement was significantly more frequent among the male than the female patients, especially in tumors of less differentiated types (diffuse type) and involving the upper stomach (P < 0.05). EBNA1 and LMP2A expression were detected in 42 (93.3%) and 24 (53.3%) cases, respectively. None expressed EBNA2, LMP1, and ZEBRA. Among 45 cases of EBV associated gastric carcinomas, DNMT1, p16 and cyclin D1 expression were seen in 35 (77.8%), 10 (22.2%), and 29 (64.4%) cases, respectively. In contrast, among 40 EBV negative gastric carcinomas, expression of the three proteins were 20 (50.0%), 25 (62.5%) and 12 (30.0%), respectively. The difference of expression of the three proteins between the two groups was significant (P < 0.05). Expression of p16 correlated with the depth of the tumor invasion. Correlated protein expression was seen between LMP2A and DNMT1, between DNMT1 and p16, and between p16 and cyclin D1 (P < 0.05). EBV associated gastric carcinoma accounts for 6.7% of gastric carcinomas in Guangzhou with the Latency I pattern in some cases and between Latency I and II in others. The correlated expression of LMP2A, DNMT1, p16 and cyclin D1 may contribute to the pathogenesis of EBV associated gastric carcinomas.

Epstein-Barr virus positivity in Hodgkin's disease does not correlate with an HLA A2-negative phenotype.

Epstein-Barr virus- (EBV) related DNA and RNA can be found in tissues involved with Hodgkin's disease, specifically in the Reed-Sternberg cells. These cells also express the membrane antigens LMP1 and LMP 2A and 2B. Studies in normal individuals indicate that cellular immunity against LMP2 was frequently mediated through human leukocyte antigen (HLA) A2, whereas responses to LMP1 appeared to be relatively infrequent. Assuming that LMP2-positive Reed-Sternberg cells would be sensitive to a CD8-positive cellular immune response, the hypothesis can be made that EBV-positive Hodgkin's disease should be more common in individuals not expressing HLA A2. To test this hypothesis, the authors have studied the frequency of HLA A2 in EBV-positive versus EBV-negative patients with Hodgkin's disease. All 72 patients diagnosed with Hodgkin's disease in Northern and Central Alberta, Canada, during 1990 and 1991 were studied. A nonisotopic in situ hybridization method with an oligonucleotide probe specific for EBER 1 and 2 was used. In addition, sections were stained for the EBV-latent protein LMP1, HLA A2, and a monomorphic HLA class I determinant and beta 2-microglobulin. EBER-positive Reed-Sternberg cells were found in 26% of the patients. The percentage of positive patients was 86% in mixed cellularity, 13% in nodular sclerosis, and 0% in lymphocyte predominance. The number of those who were HLA-A2 positive was approximately 50% in the EBV-positive and -negative patients. Therefore, no correlation between HLA A2 expression and presence or absence of EBV in the R-S cells of Hodgkin's disease was identified.