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

Abstract EN

BACKGROUND: 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.ln Upper Egypt, the clinicopathologic features and genetic changes in these tumors are still unknown.

METHODS: 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.

RESULTS: Gliomas were more common in males than females (2.5:1, p <0.001) with an average age incidence of 36.5±7.6years.

The tumors were common in the parietal and frontal regions (1.5:1, 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) p53 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 IVgliomas (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 andphMSH2 (r= -0.08, p>0.05) protein expression.

CONCLUSIONS: 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.