To elucidate the histogenesis of adenocarcinomas of the stomach, we examine
d MUC gene expression in gland-forming intramucosal neoplastic lesions. Eig
hty tumors were histopathologically assigned to 1 of the following 3 groups
based upon the Vienna classification: group A (low-grade adenoma/dysplasia
), group B (high-grade adenoma/dysplasia) and group C (intramucosal carcino
ma). Immunohistochemic staining was performed with monoclonal antibodies ag
ainst MUC2 (goblet cell mucin), MUC5AC (gastric-foveolar mucin), MUC6 (pylo
ric-gland mucin) and CD 10 (brush border). Ki-67 staining was also carried
out. An obvious difference existed in MUC gene expression between lesions i
n group A and those in groups B and C. The majority of group A lesions stro
ngly expressed intestinal markers in which proliferating cell zones were fo
rmed but generally expressed no gastric markers, whereas more than 50% of g
roups B and C tumors expressed gastric markers. These findings suggest that
group A lesions are of a stable intestinal phenotype, whereas those in gro
ups B and C are phenotypically and genotypically unstable, indicating that
the adenoma-carcinoma sequence is not a major pathway, but instead that ade
nocarcinomas arise de novo. (C) 2001 Wilev-Liss, Inc.