DELETION OF EPSTEIN-BARR-VIRUS LATENT MEMBRANE-PROTEIN-1 GENE IN JAPANESE AND BRAZILIAN GASTRIC CARCINOMAS, METASTATIC LESIONS, AND REACTIVE LYMPHOCYTES

A 30-bp deletion in the Epstein-Barr virus (EBV) latent membrane prote in 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV -associated malignant lymphomas, Information on this deletion in EBV-a ssociated gastric carcinoma (EBVaGC) is limited, The association of ga stric carcinoma (GC) with EBV was examined by EBV-encoded RNA (EBER) i n situ hybridization in 510 patients from Japan and 80 patients from B razil, We studied the prevalence of 30-bp LMP1 gene deletion in EBVaGC in Japan (29 cases) and Brazil (four cases) in comparison with the co rresponding EBER1-positive metastatic lesions in lymph nodes (10 cases ) and EBV-infected reactive lymphocytes from dissected nonmetastatic l ymph nodes (22 cases), microdissected non-neoplastic gastric mucosa of EBVaGC (five cases), and EBV-nonassociated GC (25 cases), We studied, the status of the LMP1 gene by Southern blot hybridization of polymer ase chain reaction products obtained after amplification with primers flanking the site of the deletion, We also performed EBV typing and LM P1 protein immunohistochemistry. EBV DNA was amplified by polymerase c hain reaction in 30 of 33 EBVaGC cases, 8 of 10 metastatic carcinomas, 14 non-neoplastic tissues from 27 EBVaGC cases, and 12 of 25 non-EBV- associated GC cases with EBER1-positive lymphocytes, The 30-bp LMP1 ge ne deletion was observed in 23 of 26 (88.5%) cases of EBVaGC from Japa n and two of four (50%) cases of Brazilian EBVaGC as compared with EBE R1-positive reactive lymphocytes from 11 of 14 (78.6%) EBVaGC cases an d 9 of 12 (75%) cases of non-EBV-associated GC, The variant type (the 30-bp deletion variant or nondeleted wild type) of LMP1 gene was the s ame among reactive lymphocytes, primary and secondary lesions of EBVaG C in all cases for which all three tissue types were studied (six of s ix). There was no correlation between the presence of the 30-bp deleti on with depth of cancer invasion or presence of metastasis, Type A was detected in all available EBV-positive cases, The similar high incide nce of 30-bp deletion in LMP1 gene in both carcinoma cells and reactiv e lymphocytes in EBVaGC cases suggests that this deletion may not be r elevant to the pathogenesis of EBVaGC.