An immunohistochemical study of metaplastic endocrine cells in human gallbladder cancer

In order to better understand the genesis of gallbladder cancer, we investigated the metaplastic changes and the presence of endocrine cells in mucosal tissue in the tissues of 100 patients with cholecystitis and 50 patients with gallbladder cancer.

All the tissue samples were submitted to Hematoxylin-eosin and Alcian blue-periodic acid-Schiff stain. To identify endocrine cells, we utilized Grimelius or Fontana-Masson stain. To detect intestinal hormones, we used streptavidin-biotin staining. If a given tissue sample presented with goblet cells or pseudopyloric cells, we determined that it was undergoing metaplasia. To locate a focus of endocrine cells, we used the presence of argyrophil cells and argentaffin cells.

Metaplastic changes and endocrine cells were observed in 50% or more of the studied tissues that had been sampled from the lesions of chronic cholecystitis, and from the tumor and nontumor sites of gallbladder cancer. The tissues sampled from chronic cholecystitis patients showed endocrine cells releasing gut hormones, and the incidence of tissue presenting with such hormone-secreting cells tended to increase with the degree of metaplasia. The tissues sampled from the gallbladder cancer patients also showed endocrine cells, but the incidence in these tissues was not significantly correlated with the degree of metaplasia. In the tissue sampled from gallbladder cancer patients, the degree of metaplasia and the incidence of the tissues presenting with endocrine cells was not significantly different from the corresponding results obtained from chronic cholecystitis tissues. However, tissues presenting with endocrine cells occurred more frequently in samples from nontumor sites than in samples from chronic cholecystitis sites. The incidence of metaplastic cells and of endocrine cells correlated closely with the genesis of highly differentiated cancers. Lysozyme, a nonspecific defensive factor against infections, was frequently observed in the tissues sampled from patients with chronic cholecystitis as well as those with gallbladder cancer.

Although metaplastic changes and endocrine cells were observed in the tissues of chronic cholecystitis as well as gallbladder cancer, these markers were most frequently observed in nontumor sites close to the tumors themselves, suggesting that these markers are closely involved in the genesis of gallbladder cancer.