MUC gene expression and histogenesis of adenocarcinoma of the stomach.

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.

Time-dependent expression of intestinal phenotype in signet ring cell carcinomas of the human stomach.

Signet ring cell carcinomas of the stomach are thought to arise from the proper gastric mucosa without intestinal metaplasia. It was recently reported that intestinal phenotypes appear along with tumor progression. In this study, we performed several experiments to reconsider the significance of this intestinalization in the growth of signet ring cell carcinoma. We applied mucin histochemistry with monoclonal antibodies MUC2 (Ccp58) and M1 (45M1), and paradoxical concanavalin A staining for class III mucin [PCS(III)] reaction to 29 intramucosal and 25 deeply invasive carcinomas of this type and correlated the phenotypic expression with the size of the mucosal spread and the depth of tumor invasion. It was found that the larger the size of the mucosal lesion, the more frequently the intestinal phenotypes were demonstrated. There was no significant increase in the expression of the intestinal phenotype as the tumor invaded the deeper part of the mucosa or as the intestinal metaplasia increased in the background mucosa. The intestinal expression appeared to be suppressed in the earlier phase of deep invasion. In the mucosal part of the tumor, the intestinal phenotype was often expressed regionally and incompletely, coexisting with gastric phenotypes at the cellular and the tissue levels. These findings indicate that the expression of the intestinal phenotype is a time-dependent and unstable phenomenon probably based on the accumulation of genetic changes and plays a neutral role in progression of signet ring cell carcinomas.