Abstract
PURPOSE: The fragile histidine triad (FHIT) gene has recently been proposed as being a tumor suppressor gene. FHIT gene deletions or aberrant transcripts have been identified in a variety of human malignancies, including gastric carcinomas, suggesting that FHIT may play a key role in tumor development. However, the clinical impact of FHIT mutations in gastric carcinogenesis is still debated. Our purpose was to investigate whether FHIT expression in human primary gastric carcinoma is associated with the histological type, grade or stage of the tumor. METHODS: We analyzed a well-characterized set of 137 primary gastric cancers. FHIT protein expression was evaluated in gastric mucosal samples, both from the tumor and tumor-free areas by immunohistochemistry. Furthermore, in a subgroup of 30 patients, FHIT mRNA expression was assessed by nested RT-PCR. RESULTS: Absent or reduced expression of FHIT protein correlated significantly with diffuse type ( P<0.0001), poor differentiation ( P<0.0001), and advanced stage ( P<0.0001) of gastric cancer. In contrast, FHIT protein was strongly expressed and uniformly distributed in tumor-free areas. The FHIT mRNA expression was absent or altered in diffuse and poorly differentiated carcinomas. CONCLUSION: These results show that the expression of FHIT in gastric carcinoma is related to the type, grade, and stage of the tumor. We suggest that FHIT expression may be considered a potential prognostic factor in gastric cancer.