Abnormal Expression Of Fragile Histidine Triad (FHIT), Mut S Homolog 2(MSH2) Protein And Its Clinic Significance In Human Sporadic Colorectal Carcinoma

BACKGROUND & OBJECTIVE: Frequent loss of fragile histidine triad(FHIT) expression has been reported in human gastrointestinal tract carcinomas,opinions remain divergent regarding FHIT expression in colorectal carcinoma cases. Recent studies have suggested that FHIT inactivation can be a consequence of defects in mismatch repair proteins, particularly mut S homolog 2(MSH2). This study was designed to investige the expression and clinic significance of FHIT and MSH2 protein in human sporadic colorectal carcinoma(SCC).METHODSrlmmunohistochemistry SP method was used to determine the expression of FHIT and MSH2 in surgically resected specimens of 84 SCC and its corresponding paratumous normal colorectal tissues,23 cases colonic adenomas.RESULTS: The positive expression rates of FHIT protein were 48.81%,73.91% and 100% in SCC, colonic adenomas and adjacent normal colorectal tissues,respectively. The positive expression rates of FHIT protein showed increasing trend from SCC, to colonic adenomas,to paratumour normal colorectal tissues, and the difference was statistic meaning (P<0.05).No correlation was found expression levels of FHIT with their clinicopathological features such as age,gender,tumous site and histological type(P>0.05),but is correlation with tumous invade depth, differentiation degree,Ducks ' stage and lymph node metastasis(P<0.05). Deeper invade depth,lower differentiation degree, later Ducks' stage and with lymph node metastasis tumous were significantly more likely to be reduction for FHIT protein expression .Expression levels of MSH2 expression is only related to Ducks' stage(P<0.05).FHIT protein expression was positive correlation with MSH2 protein expression in SCC(r=0.3728,P<0.01).CONCLUSIONS:(DLoss or reduction of FHIT protein expression is a frequent event and Fhit gene may be a candidate tumous suppressor gene of SCC.(2) Loss or reduction of FHIT protein expression plays an important role in the development and progression of SCC.The expression levels of FHIT protein is related to the malignant degree of SCC andmay be a valuable biological indicator for predicting the potent invasion and metastasis of SCC. (3) FHIT protein expression is in a positive correlation fashion with MSH2 protein expression,MSH2 protein possibably keep the stability of the FHIT protein in SCC.(4) Detection of banding FHIT with MSH2 expression can enhance rate of screening among high-risk population and preclinic diagnosis of colorectal carcinoma.