Decreased Fragile Histidine Triad Gene Protein Expression Is Associated With Worse Prognosis in Oral Squamous Carcinoma

Abstract

Fragile histidine triad (FHIT) gene is thought to be a tumor suppressor; abnormalities in expression have been reported in a variety of neoplasms. To determine whether abnormalities of FHIT protein expression or loss of heterozygosity in the FHIT gene were correlated with survival or other clinical parameters in patients with oral cavity squamous cell carcinoma. Fifty-three patients with initial surgical treatment of oral cavity squamous cell carcinoma were followed a minimum of 5 years or until death. The FHIT protein expression was studied by immunohistochemistry in all patients, and a subset of 20 patients was studied for allelic loss of heterozygosity and microsatellite instability using formalin-fixed, paraffin-embedded tissue. Sixty-one percent of patients whose tumors had reduced FHIT expression were dead of disease, and 37% of patients whose tumors exhibited preserved FHIT expression were dead of disease at 5-year follow-up. Log-rank analysis showed that patients retaining FHIT expression had a longer overall survival (P = .03) and disease-free survival (P = .01). The FHIT expression was not correlated with node status or clinical stage. Loss of heterozygosity was seen in 10 (50%) of 20 tumors, low levels of microsatellite instability in 4 (20%) of 20 tumors, and high levels of microsatellite instability in 1 (5%) of 20 tumors tested. The FHIT gene was associated with a worse survival outcome when its expression was reduced in patients with oral cavity squamous cell carcinoma. Loss of heterozygosity in the gene was common, but no correlation with protein expression was found. Neither loss of heterozygosity nor microsatellite instability was found to correlate with survival. Because genomic alterations involving loss of heterozygosity of the FHIT gene were not associated with protein expression in these tumors, the presence or absence of FHIT expression may be controlled by other factors.