O-6-methylguanine-DNA methyltransferase gene (MGMT) expression in human glioblastomas in relation to patient characteristics and p53 accumulation

Repair of cytotoxic DNA damage by O-6-methylguanine-DNA methyltransferase ( MGMT) is a potentially important factor of chemoresistance to chloroethylni trosoureas (CE-NUs), commonly used in the treatment of glioblastoma multifo rme (GBM). The value of p53 as a prognostic factor in GBMs remains unclear, but a possible relationship between MGMT gene expression and p53 has been suggested. To further examine these GEM characteristics in vivo, we assesse d MGMT gene expression using semi-quantitative RT-PCR and p53 alteration by immuno-histochemistry on a series of 39 GBMs. MGMT gene expression was inv ersely correlated with age (p < 0.03), consistent with the results of other s. Interestingly, tumors from male patients had higher MGMT mRNA amounts th an tumors from female patients (p < 0.03). No prognostic implication was ob served either for MGMT gene expression or for p53 accumulation. However, MG MT gene expression was significantly lower in p53-altered GEM, regardless o f the percentage of positive cells (p < 0.01). Our observation suggests tha t in human glial tumors, a low level of MGMT gene expression might promote p53 alteration, probably via mutation of its gene. Int. J. Cancer (Pred. On col.) 84:416-420, 1999. (C) 1999 Wiley-Liss, Inc.