Transforming Growth Factor (TGF)-beta I and TGF-beta Receptor II (TGF-betaRII) Expressions in Intestinal Metaplasia, Adenoma and Carcinoma of the Stomach

ABSTRACT

PURPOSE: The carcinogenesis of gastric cancer has not been fully elucidated, but several molecular biologic alterations have been found to be related with it. TGF-betaRII mutation, which is one such alteration, has been well documented in gastric cancer, but its expression patterns in cancer and preneoplastic conditions are rarely reported. For that reason, we investigated the roles of TGF-betaI and TGF-betaRII in gastric carcinogenesis by comparing the difference of expression patterns in carcinomas and adenomas of the stomach and intestinal metaplasia by using immunohistochemical staining. METHODS: Twenty-six (26) cases of intestinal metaplasia with chronic atrophic gastritis, 21 cases of the gastric adenoma, and 51 cases of gastric cancers (28 cases of the intestinal type and 23 cases of the diffuse type) were enrolled in this study. All samples were paraffin-embedded and an immunohistochemical staining was performed using the polyclonal antibody to TGF-betaI and TGF-betaRII. Their clinicopathologic features were reviewed retrospectively. RESULTS: In normal gastric tissue and intestinal metaplasia, only the basal portion of the gastric foveola was strongly reactive to TGF-betaRII. In adenomas and well-differentiated intestinal type cancer, all tumor cells were strongly positive to TGF-betaRII, but the tumor cells of poorly differentiated intestinal-type and signet ring cell (diffuse type) cancer showed unresponsive to TGF-betaRII. The TGF-betaI expressions in normal and carcinomatous lesions were similar andshowed a weak positive reaction. TGF-betaI and TGF-betaRII responsive gastric cancer showed less invasive gastric-wall infiltration. In gastric cancer, a significant correlation was present between tumor depth and response to TGF-betaI & TGF-betaRII. CONCLUSION: It is presumed that TGF-betaRII plays an important role in cell differentiation and aggressiveness in gastric cancer and that it may be useful as a prognostic factor.