Loss of fragile histidine triad protein in human hepatocellular carcinoma

To investigate the expression of fragile histidine triad (FHIT) gene protein, Fhit, which is recently thought to be a candidate tumor suppressor. Abnormal expression of fragile histidine triad has been found in a variety of human cancers, but little is known about its expression in human hepatocellular carcinogenesis and evolution.

Sections of 83 primary human hepatocellular carcionoma with corresponding para-neoplastic liver tissue and 10 normal liver tissue were evaluated immunohistochemically for Fhit protein expression.

All normal liver tissue and para-neoplastic liver tissue showed a strong expression of Fhit, whereas 50 of 83 (65.0 %) carcinomas showed a marked loss or absence of Fhit expression. The differences of Fhit expression between carcinoma and normal or para-neoplastic liver tissue were highly significant (P=0.000). The proportion of carcinomas with reduced Fhit expression showed an increasing trend (a) with decreasing differentiation or higher histological grade (P=0.219); (b) in tumors with higher clinical stage III and IV (91.3 %, P=0.000), compared with tumors with lower stage I and II (27.6 %); and (c) in cancers with bigger tumor size (>50 mm) (75.0 %, P=0.017), compared with smaller tumor size (< or = 50 mm).

FHIT inactivation seems to be both an early and a later event, associated with carcinogenesis and progression to more aggressive hepatocellular carcinomas. Thus, evaluation of Fhit expression by immunohistochemistry in hepatocellular carcinoma may provide important diagnostic and prognostic information in clinical application.