Human mismatch repair gene (hMSH2) product expression in relation to recurrence of transitional cell carcinoma of the urinary bladder

BACKGROUND: Several convincing studies have shown that the hMSH2 gene plays major roles in mismatch repair by recognizing mismatched bases and preventing mutations during DNA replication. Loss of this function may result in the accumulation of DNA replication errors or even the mutator phenotype (which may be responsible for the multiple mutations required for multistep carcinogenesis), and it has been found to affect the prognosis of patients. Thus, the authors felt that it would be of interest to study the expression patterns of hMSH2 protein in malignant tumors and to assess the correlation of hMSH2 protein to various clinical and pathologic features in these patients. METHODS: The authors examined the expression patterns of hMSH2 protein in 115 patients with transitional cell carcinoma (TCC) of the urinary bladder by immunohistochemical technique using monoclonal antibody to hMSH2 protein. RESULTS: The group in which hMSH2 was preserved (>20% of nuclei were positive for staining by anti-hMSH2 antibody) included 86 of 115 (75%) of the TCCs, whereas the remaining 29 cases (25%) belonged to the group in which hMSH2 was preserved (< or = 20% of tumor nuclei were positive), including 2 negative cases. Univariate analysis indicated that reduced expression of hMSH2 protein was significantly more frequent in high grade tumors than in low grade tumors (P = 0.04). Furthermore, statistical multivariate analysis revealed that hMSH2 reduction was significantly related to the recurrence (P = 0.02). CONCLUSIONS: These results suggest that abnormal expression of hMSH2 protein might be involved in tumorigenic processes and in the progression of some TCCs, and that the loss of hMSH2 protein expression might be a useful predictor of recurrence of TCC.