Loss of FHIT Expression in Breast Cancer Is Correlated with Poor Prognostic Markers

Abstract

The fragile histidine triad (FHIT) gene is a putative tumor suppressor gene that is thought to be involved in the carcinogenesis of breast cancer. Loss of FHIT expression has been observed in up to 72% of breast cancers and has been associated with increased p53, a high proliferation index, and increased tumor size and grade. However, loss of FHIT expression has not been investigated in association with apoptosis and cyclooxygenase-2 (COX-2) expression in breast cancer. Furthermore, expression of FHIT in primary breast tumors and their metastatic axillary lymph nodes has also not been previously described. The purpose of this study was to evaluate the expression of FHIT, COX-2, bcl-2, and p53 in primary breast tumor tissue; correlate their expression with known clinical and pathologic markers; and in cases when tissue was available, evaluate the expression of FHIT and COX-2 in the corresponding metastatic axillary lymph node in the same patient. Primary breast tumor specimens from 80 patients were examined for the presence of FHIT, COX-2, bcl-2, and p53 expression by immunohistochemistry using standard methods. When tissue was available, the expression of FHIT and COX-2 was also evaluated in the corresponding metastatic axillary lymph node specimen. FHIT expression in primary breast tumors was 56%. There was a significant correlation between FHIT expression in primary breast tumor and bcl-2 expression (P = 0.017). We also observed a significant inverse correlation between FHIT expression in primary breast tumor tissue and p53 expression (P = 0.023) in lymph node-negative cases. A significant inverse correlation between FHIT expression in the primary tumor and Ki-67 (P = 0.009) was also observed in lymph node-negative cases. FHIT expression in primary tumors correlated with FHIT expression in the metastatic lymph node (52.5%; P = 0.001). FHIT expression in primary tumors did not correlate with COX-2 expression. Our results suggest that loss of FHIT expression in breast cancer is associated with poor prognostic features. Furthermore, loss of FHIT expression is also seen in metastatic axillary lymph node. The prognostic and predictive value of these findings needs to be further evaluated in larger trials with longer follow-up.