Epstein‐Barr virus in gastric carcinoma with lymphoid stroma. Special reference to its detection by the polymerase chain reaction and in situ hybridization in 99 tumors, including a morphologic analysis

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Abstract
Gastric carcinoma with lymphoid stroma (GCLS) has been reported to have a more favorable prognosis than ordinary gastric carcinoma, however, the precise mechanism of the pathogenesis for GCLS remains unclear. The authors analyzed 99 GCLS in 94 patients for Epstein-Barr virus (EBV) sequences using polymerase chain reaction (PCR) and in situ hybridization (ISH); these were compared with 42 ordinary gastric carcinomas. Two series of PCR showed 81 (82%) and 46 (47%) of the 99 GCLS to have EBV sequences, which were significantly higher compared with ordinary gastric carcinoma (50% and 9.5%, respectively). With ISH using thymine-thymine dimerized oligonucleotide probes corresponding to EBV-encoded small RNA 1 (EBER1), 82 (83%) of 99 GCLS showed clear, intense hybridization signals localized over the nuclei of the tumor cells, in contrast to only 4 (9.5%) of 42 ordinary carcinomas (P < 0.001). A comparative morphologic analysis of EBER1-positive and negative GCLS revealed that typical features of GCLS, such as mild cellular pleomorphism, rare mitoses, a marked degree of lymphoid stroma, and mild fibrosis, together with a lymphoid infiltration within the cancer cell nests were significantly more frequent in EBER1-positive GCLS. More than 80% of GCLS were associated with EBV. The presence of EBV association in GCLS was characterized by the above morphologic features.