Cellular phenotypes of differentiated-type adenocarcinomas and precancerous lesions of the stomach are dependent on the genetic pathways

To elucidate the relationship between genetic alterations and cellular phen otypes in differentiated-type carcinomas and precancerous lesions of the st omach, mutations of p53, APC and K-ras genes were examined, as well as micr osatellite instability (MSI), in 52 tumours of the stomach. Tumours were se lected with the following phenotypical features, using mucin histochemical and immunohistochemical analyses, in addition to their morphological featur es: (1) tumours with an extremely well-preserved gastric foveolar phenotype (foveolar-type); (2) tumours with an extremely well-preserved complete-typ e intestinal metaplastic phenotype (CIM-type); and (3) ordinary tumours wit hout extreme phenotypes (ordinary-type), MSI occurred in 45% of foveolar-ty pe, 24% of ordinary-type, and 0% of CIM-type tumours, p53 gene alterations occurred in 5% of foveolar-type, 18% of ordinary-type, and 31% of CIM-type, APC gene alterations were detected in 9% of foveolar-type, 6% of ordinary- type, and 0% of CIM-type, No K-ras gene mutation was detected in any of the three types. These results indicate that the genetic pathways are quite di fferent among the phenotypes of tumours of the stomach. The 'mutator pathwa y', characterized by MSI, plays an important role in the tumourigenesis of foveolar-type, but not CIM-type tumours, The 'suppressor pathway', represen ted by p53 alteration, could participate in the tumourigenesis of the CIM-t ype, but is rare in foveolar-type tumours, Copyright (C) 2000 John Wiley & Sons, Ltd.