To elucidate the adenoma-carcinoma sequence in the stomach, we investigated Epstein-Barr virus (EBV) incorporation, p53 overexpression, and microsatellite instability (MSI) in gastric adenomas and carcinomas. The study involved 66 cases of gastric carcinomas within or adjacent to adenomas (adenoma-carcinoma cases), 81 cases of simple adenomas (without carcinoma), and 306 de novo carcinomas (without adenoma focus). EBV incorporation was revealed in 1 (1.5%) of the adenoma-carcinomas, in none of the adenomas, and in 17 (5.6%) of the de novo carcinomas. p53 overexpression was observed in 24.2% (16 of 66) of the adenomas in the adenoma-carcinoma cases and in 36.5% (23 of 63) of corresponding carcinomas (kappa = 0.63, P = 0.00). MSI was positive in 12.3% (8 of 65) of the adenomas in the adenoma-carcinoma cases and in 18.8% (12 of 64) of the corresponding carcinomas (kappa = 0.77, P = 0.00). In conclusion, EBV incorporation is not possibly associated with the gastric adenoma-carcinoma sequence, whereas the gastric adenoma-carcinoma sequence seems to be supported in terms of p53 overexpression or MSI. The transcriptional activation of EBV may occur relatively late (after the adenoma stage) in the gastric adenoma-carcinoma sequence.
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