The expression of Fhit protein is related inversely to disease progression in patients with breast carcinoma

BACKGROUND The FHIT gene, located at human chromosome 3p14.2, frequently is deleted in a number of human tumors, including breast carcinoma. Its protein product (Fhit) is presumed to have tumor suppressor function. Loss of expression of a tumor suppressor gene is an important step in tumor progression from premalignant, to in situ, to invasive carcinoma. METHODS In the current study, Fhit expression was examined in invasive carcinomas and in epithelial lesions representing stages of carcinoma progression in 50 mastectomy specimens using immunohistochemical methods. RESULTS Normal ductal and lobular epithelium consistently and strongly expressed Fhit. A complete loss of or a significant reduction in Fhit expression was observed in 72% of breast carcinomas. A statistically significant, negative correlation in Fhit expression among the stages of disease progression in Fhit negative breast carcinomas was observed (normal epithelium > hyperplasia > atypical hyperplasia and carcinoma in situ > invasive carcinoma), whereas no loss of Fhit expression in precursor lesions was observed in Fhit positive tumors. CONCLUSIONS These observations are consistent with the observed role of FHIT as a tumor suppressor gene in the pathogenesis of specific subsets of carcinomas. Cancer 2000;88:1378–83. © 2000 American Cancer Society. The expression of Fhit is reduced as the stage of disease progresses in patients with breast carcinoma. The finding is consistent with the tumor suppressor role of Fhit protein noted in breast carcinogenesis.