Loss of FHIT expression in transitional cell carcinoma of the urinary bladder

Cytogenetic and loss of heterozygosity (LOH) studies demonstrated chromosom e 3p deletions in transitional cell carcinoma (TCC), We recently cloned the tumor suppressor gene FNIT (fragile histidine triad) at 3p14.2, one of the most frequently deleted chromosomal regions in TCC of the bladder, and sho wed that it is the target of environmental carcinogens. Abnormalities at th e FHIT locus have been found in tumors of the lung, breast, cervix, head an d neck, stomach, pancreas, and clear cell carcinoma of the kidney. We exami ned six TCC derived cell lines (SW780, T24, Hs228T, CRL7930, CRL7833, and H TB9) and 30 primary TCC of the bladder for the integrity of the FHIT transc ript, using reverse transcriptase-polymerase chain reaction (RT-PCR) to inv estigate a potential role of the FHIT gene in TCC of the bladder. In additi on, we tested expression of the Fhit protein in the six TCC-derived cell li nes by Western blot analysis and in 85 specimens of primary TCCs by immunoh istochemistry, Three of the six cell lines (50%) did not show the wild-type FHIT transcript, and Fhit protein was not detected in four of the six cell lines (67%) tested. Fhit expression also was correlated with pathological and clinical status. A significant correlation was observed between reduced Fhit expression and advanced stage of the tumors. Overall, 26 of 30 (87%) primary TCCs showed abnormal transcripts. Fhit protein was absent or greatl y reduced in 61% of the TCCs analyzed by immunohistochemistry. These result s suggested that loss of Fhit expression may be as important in the develop ment of bladder cancer as it is for other neoplasms caused by environmental carcinogens.