Published in Cancer Detection and Prevention 2001; 25(3):318-324.

Alterations of the FHIT Gene in Breast Cancer: Association with Tumor Progression and Patient Survival

Sigurdur Ingvarsson, DrMedSc, Bjarnveig I. Sigbjornsdottir, BSc, Chen Huiping, MD, Jon G. Jonasson, MD, and Bjarni A. Agnarsson, MD

Department of Pathology, University Hospital, Reykjavik, Iceland.

Address all correspondence and reprint requests to: Sigurdar Invarsson, DrMedSc, Department of Pathology, University Hospital, Reykjavik, Iceland.

ABSTRACT: Our previous results on breast tumors show that LOH (los of heterozygosity) at the FHIT locus is associated with reduced FHIT protein expression. We have also shown that LOH at this locus is significantly higher in tumors from patients carrying the BRCA2 999del5 mutation than in tumors without this mutation, presumably because of lack of DNA repair. Here, our aim was to determine the relationship of FHIT LOH with breast tumor progression. Five microsatellite markers located within the FHIT gene were typed in 239 breast tumors and corresponding normal tissue, and the LOH results were compared with clinicopathologic factors and LOH at other chromosome regions. LOH at FHIT is associated with estrogen- and progesterone-negative breast tumors, 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 a 60% incresed relative risk of dying. We conclude that the loss of FHIT results in growth advantege of breast tumor cells, is associated with unstable genome and may be of prognostic value.

KEY WORDS: Breast cancer, prognostic factors, survival.