Down‐regulation of fragile histidine triad expression in prostate carcinoma

BACKGROUND The fragile histidine triad (FHIT) gene is a tumor suppressor gene that belongs to the histidine triad family of nucleoside binding proteins. The gene encompasses the common human chromosomal fragile site, the FRA3B locus at chromosome 3p14.2, and is expressed in most normal adult tissues and tumor cell lines. Numerous studies have indicated that the FHIT gene on chromosome 3p may play an important role in human neoplasia, although very few studies have investigated the FHIT gene in prostate carcinoma. METHODS Using immunohistochemical analyses, the authors studied the expression of FHIT in prostate tumors from 84 radical prostatectomy specimens to determine whether there were any correlations between FHIT expression and various clinicopathologic characteristics. RESULTS The percentages of cells stained with antibody to FHIT were significantly lower overall for tumor cells compared with normal cells (P = 0.0001). FHIT immunostaining intensity also was significantly lower for tumor cells compared with normal cells (P = 0.0001). A weak but statistically significant correlation (P = 0.045) was demonstrated with the presence of extraprostatic extension in the patient samples. No other significant correlation was seen between the percentage of cells stained for FHIT or FHIT immunostaining intensity and Gleason grade, tumor stage, tumor size, lymph node metastasis, surgical margins, vascular invasion, perineural invasion, or the presence of high‐grade prostatic intraepithelial neoplasia. CONCLUSIONS The data presented indicate a down‐regulation of the FHIT tumor suppressor gene in prostate carcinoma and, thus, propose a potential target for therapeutic intervention. Cancer 2003;97:1447–52. © 2003 American Cancer Society. DOI 10.1002/cncr.11201 Using an immunohistochemical method, the authors demonstrated a significant reduction in both the percent of cells stained with the fragile histidine triad (FHIT) antibody and the intensity of FHIT antibody staining in human prostate tumor cells compared with normal prostate cells. Taken together, these data suggest that loss of FHIT expression may be implicated in prostatic carcinogenesis, and FHIT may be a potential target for future therapeutic intervention.