Diffuse and intestinal type gastric carcinomas differ in their expression of apoptosis related proteins.

BACKGROUND: Gastric carcinomas can be divided into intestinal and diffuse types, with the last type having a worse prognosis. AIMS: To investigate whether specific patterns in the expression of apoptosis related proteins correlate with carcinoma type and/or prognosis METHODS: The expression of Fas, Bcl-2, Bax, Bcl-xl, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was studied immunohistochemically and the extent of apoptosis and proliferation was investigated in 11 cases of intestinal type and in eight cases of diffuse type carcinoma. RESULTS: Fas was expressed in all intestinal type and in one diffuse type carcinoma. Bcl-xl was expressed in 10 of 11 intestinal type and in one of eight diffuse type carcinomas. Bcl-2 was expressed in lamina propria immune cells. iNOS was expressed in six of 11 intestinal type and in four of eight diffuse type carcinomas, and COX-2 was expressed in eight of 11 intestinal type and in six of eight diffuse type carcinomas. CONCLUSION: Fas and Bcl-xl expression can differentiate between intestinal type and diffuse type gastric carcinomas. No differences in apoptosis and proliferation between intestinal type and diffuse type gastric carcinomas were observed.

Expression of apoptosis-related proteins in Barrett's metaplasia-dysplasia-carcinoma sequence: a switch to a more resistant phenotype.

Barrett's esophagus, or columnar-lined esophagus (CLE), is a premalignant disorder in which the stratified squamous epithelium is replaced by metaplastic epithelium. To gain more insight into the process of carcinogenesis in CLE, we studied several factors involved in the apoptotic pathway in biopsies with gastric metaplasia (GM), intestinal metaplasia (IM), dysplasia, and/or adenocarcinoma. Immunohistochemistry was performed for Fas, Bcl-2, Bax, Bcl-xl, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). Fas staining was positive in the epithelium of all biopsies from patients with CLE but negative in normal gastric mucosa. Fas staining was positive in all tumor cells of the 8 cases containing adenocarcinoma. Bcl-2 was positive in lamina propria immune cells of all specimens. Bax staining was positive in the epithelium of all biopsies, including tumor cells. Bcl-xl was positive in dysplasia and tumor cells, but negative in 8 of 17 biopsies containing IM. iNOS was positive in 20 of 21 biopsies with IM and in 4 of 8 dysplasia biopsies. COX-2 was positive in 7 of 8 adenocarcinomas. We conclude that the apoptotic balance in the transformation from IM to adenocarcinoma switches to an antiapoptotic phenotype because of increased Bcl-xl expression and decreased Bax expression. Fas can be used as a marker for the differentiation of gastric mucosa and metaplasia in the esophagus. iNOS is highly positive in CLE-associated intestinal metaplasia. COX-2 is negative in nonmalignant CLE. Therefore, pharmacologic inhibition of COX-2 activity is unlikely to be effective in the preventing CLE-associated adenocarcinoma. There was no clear correlation between iNOS expression and activation of proapoptotic and antiapoptotic genes.