Expression and role of HMSH2 P53 and BCL-2, in human gliomas in upper Egypt

ABSTRACT

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 involves interactions among p53, Bcl-2 and hMSh2 proteins. In Upper Egypt, the clinicopathologic features and genetic changes in these tumors are still unknown. To test our hypothesis and to examine these issues, 60 specimens entailing normal brain tissues, gliosis and gliomas [grade I, II, III, IV] were immunostained for p53, Bcl-2 and hMSH2 protein expression. Gliomas were more common in males than females [2.51, p <0.001] with an average age incidence of 36.5 +/- 7.6 years. The tumors were common in the parietal and frontal regions [1.51, respectively]. As compared to the normal brain and gliosis, examination of the average weighted scores in gliomas [grade I, II, III, IV, respectively] showed significant upregulation of 1] p.53 proteins [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], 2] hMSH2 [5.3 +/- 1.3; 1.9 +/- 1.1; 1.5 +/- 0.7; 2.2 +/- 0.5; 4.1 +/- 1.5 and 4.7 +/- 1.1, p< 0.0006] and 3] Bcl-2 [0.8 +/- 0.5; 2.0 +/- 0.6; 1.9 +/- 0.6; 1.9 +/- 0.5; 4.4 +/- 1.2, p< 0.001]. Alternatively, downregulation of Bcl-2 immunoreactivity score occurred in grade IV gliomas [0.9 +/- 0.5, p< 0.0001]. There was an insignificant negative correlation between p53 and Bcl-2 [r=-0.07, p>0. 05] and between p53 and phMSH2 [r=-0.08, p>0.05] protein expression. In Upper Egypt 1] gliomas had similar clinicopathologic features to those in the high risk regions, and 2] alterations of the p53, Bcl-2 and hMSH2 proteins occur during the development of these tumors