The Loss of Heterozygosity of FHIT Gene in Sporadic Breast Cancer

Lisiane Silveira Zavalhia (Research Laboratory in Pathology, Graduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil)
Andrea Pires Souto Damin (Department of Gynecology and Obstetrics of Federal University, Rio Grande do Sul (UFRGS), Porto Alegre, Brazil)
Grasiela Agnes (Research Laboratory in Molecular Biology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Rio Grande do Sul, Brazil)
Aline Weber (Research Laboratory in Pathology, Graduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil)
Taís Frederes Kramer Alcalde (Research Laboratory in Pathology, Graduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil)
Laura Marinho Dorneles (Research Laboratory in Pathology, Graduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil)
Guilherme Watte (Department of Respiratory Medicine and Thoracic Surgery, Irmandade da Santa Casa de Misericordia de Porto Alegre, Rio Grande do Sul, Brazil)
Adriana Vial Roehe (Department of Pathology, Graduate Programa in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil)


The loss of heterozygosity (LOH) is a genetic event that can change gene function. FHIT is a potential tumor suppressor gene.  Although the precise FHIT molecular mechanism of action is not well understood, evidences suggest that Fhit protein reduced levels are involved in mammary carcinogenesis.  The aim of this study was to investigate if FHIT LOH could influence on sporadic breast cancer (BC) biological behavior, through its association with prognostic factors for sporadic BC.

Tumor tissue and peripheral blood samples were analyzed using the microsatellite marker D3S1300. The findings were associated with clinicopathological parameters including overall survival. LOH was detected in 31.1%(52/167) of the informative BC’ cases. Considering clinical and pathological characteristics we have found no significant association with FHIT LOH status. The mean follow-up time was 80 months. After the Cox regression analysis two parameters remained associated with BC’s risk of death: TNM stage III and IV - HR = 3.74(95% CI, 1.16-12.1) P=0.027 and disease relapse HR = 3.14(CI 95% 1.26-7.80) P =0.014. 

This study shows that FHIT LOH by itself is not a prognostic factor for sporadic BC.  Further researches are required to elucidate the functional role of FHIT LOH concerning to BC. 


Breast cancer; D3S1300; LOH; Survival; Loss of heterozygosity

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Copyright © 2021 Lisiane Zavalhia, Andrea PS Damin, Grasiela Agnes, Aline Weber, Tais FK Alcalde, Laura Dorneles, Guilherme Watte, Adriana Vial Roehe

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