The Expression And Significance Of DNA Mismatch Repair Gene HMLH1 In Transitional Cell Carcinoma Of Bladder

Objective To determine the expressions of DNA mismatch repair gene hMLH1 protein in transitional cell carcinoma of bladder(TCC), and assess the correlations between hMLH1and various clinical and pathologic features.Methods From March, 1996 to December, 2008, 120 examples paraffin wax specimen of bladder carcinoma and 25 healthy controls were collected in First Affiliated Hospital of Henan Scientific and Technical University. 86 cases were male and 34 women, aged 23-81 years, mean age 60.3 years. There were no preoperative chemotherapy, radiotherapy history. Histology grade (graduation of WHO 1973): The transitional cell carcinoma was divided into third-level, namely high differentiation (G_l,n=36), middle differentiation(G₂,n=50) and low differentiation(G₃,n=34),which was according to tumor cell's size, the shape, the nucleus change, the fission state. The urinary bladder carcinoma stages (UICC 2002 TNM) were divided into two groups, including Ta-T₁ (n=79) and T₂-T₄ (n=41).Twenty examples normal urinary bladder specimen to make the control. Expression of DNA mismatch repair gene hMLH1 protein was examined in urinary bladder specimens from 120 carcinoma bladder patients and 25 healthy controls by immunohistochemical method. In addition, the difference of hMLH1 expression levels in carcinoma bladder was compared and evaluated the correlations of it with histology grade and clinical stage of bladder carcinoma. The empirical datum analysis applies with the SPSS16.0 statistical analysis software.Results Expression of hMLH1 was exclusively restricted to the crypt nuclei. hMLH1 low expression was identified in 39/120 (32.5%) carcinoma bladder patients and high expression in 81/120 (67.5%). Loss of hMLH1-low expression was found in 25 healthy controls, significantly lower than that in bladder carcinoma group (P< 0.05). Statistical analysis using chi-square showed the expression level of hMLH1 was significant higher for T₂-T₄ tumor(51.2%) than Ta-T₁(22.8%) (x²=9.948,p<0.05). The difference of expression level of hMLH1 among G1,G2 and G3 of TCC possessed statistics significance, and a difference of statistical significance (x²=9.497,p<0.05). Mismatch repair gene hMLH1 protein absence in different age groups and gender expression not significantly different, indicating that the expression of hMLH1 protein deficiency and age and gender.Conclusion Expression of hMLH1 is exclusively restricted to the crypt nuclei. The result shows that DNA mismatch repair gene hMLH1 protein may play an important role in the crypt nuclei. Reduced expression rate of hMLH1 in transitional cell carcinoma of bladder is significantly higher than that in control group and the DNA mismatch repair gene hMLH1 correlated with development of bladder carcinoma. Reduced expression of hMLH1 in transitional cell carcinoma of bladder is also correlated to differentiation degree and clinical stage. Least differentiated and most advanced tumors are more likely to have reduced hMLH1 expression, which may contribute to the development of a subset of TCCs owning to genetic mutation.