Absence of Msh2 protein expression is associated with alteration in the FHIT locus and Fhit protein expression in colorectal carcinoma

Frequent loss of Fhit expression has been reported in human gastrointestina l tract carcinomas; opinions remain divergent regarding Fhit expression in colorectal carcinoma (CRC) cases. Recent studies have suggested that Fhit i nactivation can be a consequence of defects in mismatch repair proteins, pa rticularly Msh2. Immunohistochemical analysis of Msh2 and Fhit protein expr ession in 62 CRC cases was performed. The same CRCs were examined for allel ic loss at three loci within or near FHIT and for FHIT mRNA expression by r everse transcription-PCR amplification. Half of the 62 CRC cases were posit ive for Fhit protein. Fhit protein loss correlated significantly with the p rogression of carcinoma (P < 0.01) as well as lymph node metastasis (P < 0. 05). Loss of Msh2 protein correlated significantly with loss of Fhit protei n (P < 0.05) and FHIT locus alteration (P < 0.05). Loss of Fhit protein exp ression was observed in 50% of sporadic CRCs and was significantly more fre quent in more advanced cancers. Interestingly, alteration of the fragile FH IT locus and loss of Fhit protein expression were significantly more freque nt in sporadic CRCs lacking Msh2 protein, suggesting that this mismatch rep air protein may be important in maintaining the integrity of the common fra gile locus within the FHIT gene.