MUC gene expression and histogenesis of adenocarcinoma of the stomach

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Abstract
To elucidate the histogenesis of adenocarcinomas of the stomach, we examined MUC gene expression in gland‐forming intramucosal neoplastic lesions. Eighty 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 carcinoma). Immunohistochemic staining was performed with monoclonal antibodies against MUC2 (goblet cell mucin), MUC5AC (gastric‐foveolar mucin), MUC6 (pyloric‐gland mucin) and CD10 (brush border). Ki‐67 staining was also carried out. An obvious difference existed in MUC gene expression between lesions in group A and those in groups B and C. The majority of group A lesions strongly expressed intestinal markers in which proliferating cell zones were formed but generally expressed no gastric markers, whereas more than 50% of groups B and C tumors expressed gastric markers. These findings suggest that group A lesions are of a stable intestinal phenotype, whereas those in groups B and C are phenotypically and genotypically unstable, indicating that the adenoma‐carcinoma sequence is not a major pathway, but instead that adenocarcinomas arise de novo.