Gastric phenotypic expression in human gallbladder cancers revealed by pepsinogen immunohistochemistry and mucin histochemistry.

Gastric phenotypic expression indicated by paradoxical concanavalin A (Con A) staining for class III mucins and the immunoperoxidase method for pepsinogen (Pg) I and Pg II was found in pyloric gland metaplasia of gallbladder epithelium. Using the same methods, the features of gallbladder cancers and their relationship to pyloric gland metaplasia in the human gallbladder epithelium were studied. Histologically, 57 gallbladder cancers were classified into 5 papillary adenocarcinomas, 29 tubular adenocarcinomas, 8 poorly differentiated adenocarcinomas, 6 signet-ring cell carcinomas, 4 mucinous adenocarcinomas, and 5 squamous cell carcinomas. In papillary and tubular adenocarcinomas, Pg I and/or Pg II staining was detected in 80% and 75.9% of cancers, respectively. Pg II staining was significantly more frequent than Pg I staining. One signetring cell carcinoma also had Pg II activity. Pyloric gland metaplasias all contained class II mucins and were further classified into complete type and incomplete type on the basis of presence or absence Pg I and/or Pg II activities. A few cancer cells with class III mucins were negative for Pg staining; conversely, a few cells with Pg I and/or Pg II had no class III mucins. Phenotypic diversity in both class II mucin reactivity and Pg activities was observed in gallbladder cancer cells with the pyloric gland cell type. By comparison, pyloric gland metaplasia varied only in Pg activities. A few Pg-positive cancers were found in the gallbladder with Pg-negative pyloric gland metaplasia. The present results clearly indicate the appearance of gastric phenotypic expression in both gallbladder epithelium and gallbladder cancers and suggest the independent induction of pyloric gland metaplasia and cancer with gastric phenotypic expression.