Loss of fragile histidine triad expression in colorectal carcinomas and premalignant lesions

Abnormal expression of the fragile histidine triad (FHIT) candidate tumor s uppressor gene has been observed in a variety of human tumors, but little i s known about its expression during colorectal tumorigenesis. Sections of 7 0 aberrant crypt foci (ACF), 55 adenomas, 84 primary colorectal carcinomas, and 13 metastatic lesions were evaluated immunohistochemically for Fhit ex pression. All normal colonic epithelium showed a strong expression of Fhit; 44% of carcinomas shelved a marked loss or absence of Fhit expression. The proportion of carcinomas with reduced expression showed an increasing tren d (a) with decreasing differentiation and (b) in tumors with metastases (62 %) compared with tumors without metastases (38%). The proportion of metasta tic lesions (12 of 13) with reduced expression of Fhit was even greater. Al though only a small proportion of ACF and adenomas showed a reduction of Fh it expression, the reduced expression of Fhit was strongly associated with the degree of dysplasia in both ACF (P = 0.0002) and adenomas (P = 0.0085), The findings of reduced expression of Fhit in a small proportion of coloni c precancerous lesions and in increased proportions of primary and metastat ic colorectal cancers suggest that Fhit plays a role in the development and progression of some colon carcinomas.