Association of distinctive Epstein-Barr virus variants with gastric carcinoma in Guangzhou, southern China.

To investigate the clinicopathologic features, Epstein-Barr virus (EBV) latency pattern and genome polymorphism of EBV-associated gastric carcinoma (EBVaGC) in Guangzhou, an endemic area of nasopharyngeal carcinoma (NPC), an in situ hybridization assay of EBV-encoded small RNA-1 (EBER-1) was used to identify the presence of EBV in 676 consecutive gastric carcinoma cases. EBV-encoded proteins EBNA1, EBNA2, LMP1, and ZEBRA were detected by immunohistochemistry. EBV genome polymorphism was also analyzed by PCR and DNA sequencing. Of the 676 cases, 45 EBV-positive cases (6.7%) were identified, including 37 (8.5%) male and 8 (3.3%) female cases. EBNA1 was detected in 42 cases (93.3%), while EBNA2, LMP1, and ZEBRA were all negative. In the EBV genome polymorphism analysis, type A strain, prototype F, type I, XhoI-, and del-LMP1 variants were predominant among EBVaGC patients, accounting for 44 (97.8%), 37 (82.2%), 45 (100%), 34 (75.6%), and 42 (93.3%) cases, respectively. Moreover, a new hotspot mutation in the BamHI-W1/I1 boundary region (148,972 T --> C) was found in 39 (86.7%) of the 45 cases. The predominant EBV variants in EBVaGC in Guangzhou are prototype F, type I, and XhoI-, which are different from those in NPC in this area (predominant variant-type "f") and in EBVaGC in Latin American countries (predominant type "i" and XhoI+), suggesting that the EBV variants are not only geographically distributed but also disease restricted, and the pathogenic role of EBV in different EBV associated epithelial malignancies in different areas may be distinct.