Alteration of the FHIT gene in breast cancer: association with tumour progression and patient survival

AIMS We have previously shown that LOH at the FHIT locus is higher in ductal (59%) than lobular (16%) breast cancer. Also, LOH of FHIT is even higher (75%) in tumours from patients carrying BRCA2 mutation, presumably due to lack of DNA repair. LOH of FHIT in all these breast tumour types is associated with reduced Fhit protein expression. Now our aim is to analyze if the FHIT LOH is associated with breast tumour progression. METHODS Five microsatellite markers located within the FHIT gene were analyzed in 230 breast tumours and corresponding normal tissue and the LOH results were compared to clinicopathological factors and LOH at other chromosome regions in our database. RESULTS LOH at FHIT is associated with ER and PR negative breast tumours, high S-phase fraction, reduced patient survival and LOH at chromosome regions 6q, 7q, 8p, 9p, 11p, 11q, 13q, 16q, 17p, 17q, 18q and 20q. A multivariate analysis shows that LOH at FHIT results in 50% increased relative risk of dying. CONCLUSION FHIT is a tumour suppressor gene and its loss results in growth advantage of breast tumour cells. FHIT LOH is associated with unstable genome and may be of prognostic value.