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 pr oper gastric mucosa without intestinal metaplasia. It was recently reported that intestinal phenotypes appear along with tumor progression. In this st udy, we performed several experiments to reconsider the significance of thi s 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)] re action to 29 intramucosal and 25 deeply invasive carcinomas of this type an d 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 t he mucosal lesion, the more frequently the intestinal phenotypes were demon strated. There was no significant increase in the expression of the intesti nal phenotype as the tumor invaded the deeper part of the mucosa or as the intestinal metaplasia increased in the background mucosa. The intestinal ex pression appeared to be suppressed in the earlier phase of deep invasion. I n the mucosal part of the tumor, the intestinal phenotype was often express ed regionally and incompletely, coexisting with gastric phenotypes at the c ellular and the tissue levels. These findings indicate that the expression of the intestinal phenotype is a time-dependent and unstable phenomenon pro bably based on the accumulation of genetic changes and plays a neutral role in progression of signet ring cell carcinomas.