Clinicopathological significance of FHIT protein expression in stage I non-small cell lung carcinoma

Abnormalities in structure and expression of the FHIT gene have been detect ed in a considerable fraction of primary lung tumors, Previous reports indi cated that FHIT gene alterations can be simply detected by immunohistochemi cal methods. Therefore, me investigated the association of Fhit expression with clinicopathological features and allelic imbalance (AI) at the FHIT lo cus in 105 stage I non-small cell lung cancers (NSCLC) by the immunohistolo gical method and PCR analysis, Thirty-six of 105 (34%) tumors showed marked reduction of Fhit immunoreactivity, Fhit expression was markedly reduced i n most squamous cell carcinomas (24 of 28, 86%), whereas such a reduction w as detected only in a small subset of adenocarcinomas (7 of 67, 10%; P < 0. 001), A marked reduction of Fhit protein expression was observed more frequ ently in patients with a smoking history (32 of 80, 40%) than in patients w ithout a smoking history (4 of 25, 16%; P = 0.013), These results indicate that FHIT gene alterations preferentially occur in squamous cell carcinomas and in smokers. Furthermore, a reduction of Fhit protein expression in tum or cells was associated with a poorer survival of patients with stage I NSC LC, irrespective of histological subtypes of tumors (P = 0.005; log-rank te st). Fhit expression was reduced preferentially in tumors with AI at the FH IT locus; however, AI at the FHIT locus did not correlate with patients' su rvival (P = 0.262; Log-rank test). These results suggested that Fhit protei n expression could be a useful molecular marker for the prognosis of patien ts with surgically resected stage I NSCLC.