Microsatellite instability (MI), the phenotypic manifestation of mismatch repair failure, is detectable in a wide variety of human cancers. It is particularly seen in patients with the hereditary non-polyposis colon cancer (HNPCC) syndrome, in which the affected individual is at risk of developing carcinoma both at an early age and at a range of sites such as the colon, endometrium, urinary tract and stomach (Aaltonen et al, 1993;Marra and Boland, 1995;Lynch et al, 1996). Germline mutation in one of the DNA mismatch repair genes is responsible for a significant proportion of individuals affected by this syndrome (Fishel et al, 1993;Bronner et al, 1994;Liu et al, 1994;Nicolaides et al, 1994;Papadopoulos et al, 1994). MI has also been detected in a variable proportion of the sporadic form of cancer arising in these organs (Eshleman and Markowitz, 1995).Although gastric cancer, worldwide, is deemed to be both the second most common malignancy and second leading cause of cancer death Pisani et al, 1993), the incidence varies markedly in different populations. The incidence of molecular genetic changes is known to vary; for example, the series of reports from high incidence areas such as Japan, Italy, Portugal and Korea show a range for MI varying from 15% to 39% (Han et al, 1993;Chong et al, 1994;Rhyu et al, 1994;Strickler et al, 1994;Lin et al, 1995;Chung et al, 1996;dos Santos et al, 1996;Ohue et al, 1996;Renault et al, 1996). Although MI was noted in a high percentage of gastric cancers with a positive family history (Akiyama et al, 1996;Keller et al, 1996;Ottini et al, 1997), germline or somatic mutations of the mismatch repetition and repair (MMR) genes were rarely reported (Akiyama et al, 1996;Keller et al, 1996). Thus, the mechanism leading to the mismatch repair failure in gastric carcinomas remains largely unknown.The association between EpsteinÐBarr virus (EBV) and gastric cancer also varies among different populations, with the highest positive association occurring in Caucasian populations (Shibata and Weiss, 1992;Ott et al, 1994) and a low association seen in the Japanese (Tokunaga et al, 1993). EBV is found in more than 80% of a specific histological variant of gastric carcinoma, variably termed lymphoepithelioma-like carcinoma (LELC), medullary or gastric carcinoma with lymphoid stroma (Nakamura et al, 1994). This variant is characterized by the presence of a poorly differentiated morphology, a circumscribed border, an intense lymphoid reaction and a better prognosis (Watanabe et al, 1976). The possible relationship between EBV, MI and LELC is largely unexplored except in one study from Japan, in which all eight EBV-associated gastric cancers were negative for MI (Chong et al, 1994).Previous data have shown that the mutator phenotype conferred by MI has a significant role in carcinogenesis, in which it targets Microsatellite instability, EpsteinÐBarr virus, mutation of type II transforming growth factor β receptor and BAX in gastric carcinomas in Hong Kong Chinese Summary Microsatellite instability (M...