[Loss of fragile histidine triad expression and metastasis in breast cancer]

Fragile histidine triad(FHIT), a tumor suppressor candidate gene, encompasses FRA3B, a common region with the highest fragility in the human genome, and is altered in a large number of human cancers, particularly those of epithelial cell origin and associated with known carcinogenic agents. The aim of this study was to investigate the expression of FHIT protein, Fhit and the possible relationship between Fhit expression and clinicopathological indices in breast cancer.

Fhit protein expression in 66 cases of formalin-fixed, paraffin-embedded breast cancer composed of 6 in situ and 60 invasive ductal carcinoma were detected with citrate-microwave-Streptavidin-HRP(SP) immunohistochemical method, using rabbit antibody to human FHIT gene protein and relationships to invasion and lymphatic metastasis were analyzed.

Thirty-eight (57.6%) cases of carcinomas showed a marked loss or absence of Fhit expression compared with the adjacent non-cancerous breast tissues, in which 22 cases were negative. The remain 18 (27.3%) showed stronger than, and 10 (15.2%) equal to the Fhit expression of the adjacent non-cancerous tissue. The lower expression of Fhit was found in 20/24(83.3%) cases with local or axillary lymphatic metastasis, and in 18/36 (50%) cases without metastasis in the invasive ductal carcinoma. Fhit expression was determined in all 6 cases of in situ ductal carcinoma did not show lower than non-cancerous tissue. There was a significant difference in the expression of Fhit between the breast cancers with and without lymphatic metastasis, both in ductal carcinoma (P < 0.01) and in invasive ductal carcinoma(P < 0.01).

The expression of Fhit is associated with invasion and metastasis of tumor in breast cancer. It is suggested that decreased Fhit expression may play an important role in the development and progression of the tumor, and thus may become a new prognostic marker for breast cancer.