Clinicopathological Significance of Fragile Histidine Triad Transcription Protein Expression in Breast Carcinoma

The fragile histidine triad ( Fhit ) gene, which is frequently lost in many cancers, was identified as a candidate tumor suppressor gene at chromosome 3p locus 14.2. Loss of Fhit expression is an important step in tumor progression from premalignancy, to in situ , to invasive breast carcinoma. To determine whether the absence of Fhit protein correlates with other established pathological-clinical parameters or prognosis, we assessed Fhit expression using immunohistochemistry in 166 invasive breast carcinomas. Lost or significantly decreased Fhit protein expression was identified in 70 cases (42.2%). Fhit expression was inversely correlated with histological grade ( P < 0.0001), negative estrogen receptor status ( P = 0.0016), p53 overexpression ( P = 0.0040), and tumor proliferation activity ( P = 0.0006). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that reduced expression of Fhit was associated with a poor outcome ( P = 0.0086, by log-rank test). Multivariate analysis using the stepwise Cox proportional hazard model showed that lymph node metastasis was related to poor survival rates; in addition, patients with loss of Fhit expression still tended to have poor survival ( P = 0.0563). Therefore, loss of Fhit expression is associated with higher malignant phenotypes and appears to be a prognostic factor in breast carcinoma.