Fhit expression in gastric adenocarcinoma - Correlation with disease stageand survival

BACKGROUND. The FHIT gene is inactivated by deletion in a large fraction of human rumors, including gastric carcinomas, and the Fhit protein has been proposed to act as a tumor suppressor in multiple tumor types. A large frac tion of gastric adenocarcinomas have lost expression of the candidate tumor suppressor protein, Fhit, whereas normal gastric epithelial cells are stro ngly positive and Fhit loss has been found to correlate with alterations of the FHIT locus. Because the majority of gastric tumors in the current stud y were found to be entirely negative for Fhit protein, it is possible that alteration of the carcinogen-susceptible fragile region within the FHIT gen e is an early event in gastric carcinoma, as it is in lung carcinoma. METHODS. To determine whether the absence of Fhit protein correlates with e xpression of tumor markers or with clinical parameters, such as grade, stag e, and survival time, the authors assessed Fhit expression using immunohist ochemistry in a well characterized set of 55 gastric adenocarcinomas resect ed over several years, with longitudinal follow-up of patients for outcome. RESULTS. In this set of 55 gastric cancers, the absence of Fhit protein cor related with higher tumor stage (P = 0.003) and higher histologic grade (P = 0.007). In addition, patients whose tumors had lost expression of Fhit di ed of disease significantly earlier than those with Fhit positive tumors (P = 0.017). The absence of Fhit expression did nor correlate with the expres sion of any tumor markers. CONCLUSIONS. Larger studies will be required to elucidate further the relat ion between tumor stage, grade, and Fhit loss and to determine whether incl usion of Fhit antiserum in immunophenotyping of gastric adenocarcinomas wil l be a useful indicator of postdiagnosis prognosis. Cancer 2000;88:24-34, ( C) 2000 American Cancer Society.