Tumorigenesis involves alterations in the tumor suppressor genes (p53), protooncogenes (BCL-2), and housekeeping genes (human MutS homologue-2 (hMSH2). We hypothesized that development of gliomas is associated with alterations of p53, BCL-2, and hMSH2 protein expression. To test our hypothesis and to examine these issues, we immunostained 60 specimens entailing normal brain tissues, gliosis, and gliomas (Grade I, II, III, IV) for p53, BCL-2, and hMSH2 protein expression. As compared with the normal brain and gliosis, examination of the average weighted scores in gliomas (Grade I, II, III, IV, respectively) showed significant up-regulation of: (i) p53 protein (0.0 +/- 0.0; 0.0 +/- 0.0; 0.9 +/- 0.5; 1.6 +/- 0.8; 1.7 +/- 0.5; and 4.1 +/- 0.8, P < 0.0001) (ii) hMSH2 (1.3 +/- 0.3; 1.5 +/- 0.7; 1.9 +/- 1.1; 2.2 +/- 0.5; 4.1 +/- 1.5; and 4.7 +/- 1.1, P < 0.0006), and (iii) BCL-2 (0.8 +/- 0.5; 1.9 +/- 0.5; 1.9 +/- 0.6; 2.0 +/- 0.6; 4.4 +/- 1.2; and 4.6 +/- 0.8, P < 0.001). The expression values (p53, BCL-2, and hMSH2) were statistically significantly higher (P < 0.05) in astrocytomas (Grade III) than in other gliomas. There was an insignificant negative correlation between p53 and BCL-2 (r = -0.07, P > 0.05) and between p53 and hMSH2 (r = -0.08, P > 0.05) protein expression. Alterations of the p53, BCL-2, and hMSH2 proteins occur during the development of these tumors.