Increased hMSH2 protein expression in glioblastoma multiforme

Abstract

hMSH2 and hMLH1 are the most commonly studied mismatch repair proteins and their absence is associated with microsatellite instability (MSI) especially in hereditary non-polyposis colorectal cancer, and also in some sporadic tumors. However, there are some tumors, namely, urothelial neoplasms and salivary gland tumors, where overexpression of the proteins has been reported, though the implications of these findings are not very clear. There is no report on the expression of these proteins in different grades of human astrocytic tumors. We have studied the expression pattern of hMSH2 and hMLH1 in high (Grade IV, glioblastoma multiforme (GBM)) and low (Grade II, astrocytoma (AS)) grade primary human gliomas by immunohistochemistry. We observed that there was a significantly higher expression of hMSH2 protein in 28 GBM (mean 703.07 ± 236.28) as compared with 27 AS (mean 307.03 ± 204.71), p=1.47 × 10⁻⁸ by a two-tailed t-test of unpaired samples. However, for hMLH1 no such difference was observed, mean counts being 543.29 ± 320.35 for 27 GBM and 505.92 ± 342.37 for 26 AS, p=0.67. A small proportion of tumors was observed to be immunonegative for either of the proteins in both high-and low-grade tumors. While MSI has been shown previously to be infrequent in human astrocytic tumors, the implications of the overexpression of hMSH2 in GBM are not clear.