BACKGROUNDFragile histidine triad (FHIT) gene, a candidate tumor suppressor gene, is recently identified at chromosome 3p14.2, spanning the FRA3B common fragile site. Abnormalities in expression of FHIT gene have been reported in a variety of human tumours including lung cancer. The aim of this study is to investigate the expression of FHIT gene in precancerous lesions and primary lung cancer and to analyze the role of FHIT gene in lung tumorigenesis.

METHODSFHIT protein expression was detected in 298 cases of formalin fixed paraffin-embedded human samples by immunohistochemistry, including 51 precancerous lesions, 161 lung cancer samples, 30 normal lung tissue samples, 23 pulmonary benign lesion tissues and 33 metastatic lymph nodes.

RESULTSAll the normal lung tissues and pulmonary benign lesions showed positive FHIT protein expression, while the negative rate of FHIT protein expression in precancerous lesions, lung cancer tissues and metastatic lymph nodes was 54.9%, 59.0% and 78.8% respectively. Negative rate of FHIT protein in metastatic lymph nodes, lung cancer tissues and precancerous lesions was significantly higher than that in normal lung tissues and pulmonary benign lesions (P < 0.001). The expression of FHIT gene was closely related to histological classification, cell differentiation, pTNM stages and lymph node metastasis in lung cancer (P < 0.05). A marked reduction of FHIT protein expression was observed in patients with smoking history than that in patients without smoking history (P < 0.01). Furthermore, FHIT protein expression level in lung cancer was associated with survival of patients (P < 0.01).

CONCLUSIONSThese results suggest that FHIT protein expression may occur at early stage of lung carcinogenesis and be associated with the oncogenesis and progression of cancer. The correlation between cigarette smoking and FHIT expression suggests a role of FHIT in the initiation of smoking-related lung tumorigenesis.