Differentiation towards gastric foveolar, mucopeptic and intestinal goblet cells in gallbladder adenocarcinomas

Cellular differentiation in 22 surgically removed adenocarcinomas of the gallbladder was immunohistochemically studied with antibodies specific to mucins of gastric foveolar cells (M1), (pseudo)pyloric cells (M2) and intestinal goblet cells (M3), and also with antibodies against pepsinogen II and chromogranin A. More than 70% of tumours (16 of 22 cases) displayed gastric- and/or intestinal-type differentiation, most of which (12 of 16 cases) showed both types of differentiation. Two tumours showed an organoid growth pattern similar to the normal gastric mucosa. The presence of endocrine cells positive for chromogranin A was closely related to that of gastric- and/or intestinal-type cells. The present findings clearly indicate the multidirectional differentiation of gallbladder adenocarcinomas and suggest that most gallbladder adenocarcinomas develop and progress under induction of gastric and intestinal differentiation.