Fhit expression in gastric adenocarcinoma

Abstract

The FHIT gene is inactivated by deletion in a large fraction of human tumors, including gastric carcinomas, and the Fhit protein has been proposed to act as a tumor suppressor in multiple tumor types. A large fraction of gastric adenocarcinomas have lost expression of the candidate tumor suppressor protein, Fhit, whereas normal gastric epithelial cells are strongly positive and Fhit loss has been found to correlate with alterations of the FHIT locus. Because the majority of gastric tumors in the current study were found to be entirely negative for Fhit protein, it is possible that alteration of the carcinogen-susceptible fragile region within the FHIT gene is an early event in gastric carcinoma, as it is in lung carcinoma. To determine whether the absence of Fhit protein correlates with expression of tumor markers or with clinical parameters, such as grade, stage, and survival time, the authors assessed Fhit expression using immunohistochemistry in a well characterized set of 55 gastric adenocarcinomas resected over several years, with longitudinal follow-up of patients for outcome. In this set of 55 gastric cancers, the absence of Fhit protein correlated with higher tumor stage (P = 0.003) and higher histologic grade (P = 0.007). In addition, patients whose tumors had lost expression of Fhit died of disease significantly earlier than those with Fhit positive tumors (P = 0.017). The absence of Fhit expression did not correlate with the expression of any tumor markers. Larger studies will be required to elucidate further the relation between tumor stage, grade, and Fhit loss and to determine whether inclusion of Fhit antiserum in immunophenotyping of gastric adenocarcinomas will be a useful indicator of post-diagnosis prognosis.