CHARACTERIZATION OF CANCER STEM CELLS IN PATIENTS WITH BRAIN ASTROCYTOMAS: A CLINICO-PATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY

Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a variety of markers including Nestin, which can be potentially used as therapeutic targets. Dysregulation of the intermediate filament protein Nestin, the tumor-suppressor gene TP53, and Ki67 labeling index are implicated in glioma genesis and therapeutic resistance. Aim: This study aimed at evaluating the expression of Nestin –a putative cancer stem cell marker-and TP53 -a tumor suppressor gene- in astrocytomas and distinguishing their relations to different clinicopathological parameters pertinent to both the tumor and the host. Methods: The study included 40 patients (22 males and 18 females) with a mean age of 52.5 ± 11.4 years (range; 26-70 years) who were operated for brain astrocytomas. Immunohistochemical staining for Nestin, TP53, and Ki 67 was carried out on paraffin embedded tissue samples from the resected gliomas. Scores for markers expression were statistically correlated with patients age and gender, tumor grade, and patients survival. Results: Nestin staining scores ranged between 2 and 9 (mean; 6.30 ± 2.83) while those of TP53 ranged between 1 and 4 (mean; 2.50 ± 0.99). Ki 67 labeling index ranged between 3 and 48% (mean; 22.92% ± 11.48%). Ki 67 expression increased significantly with patient’s age (rho= 0.34, P=0.03) while the correlations of age with Nestin and TP53 scores were not statistically significant (rho= 0.29 and 0.11, P=0.07, 0.49, respectively). No significant associations were detected between any of Nestin, TP53 or Ki 67 scores and gender (P= 0.86, 0.46 and 0.79, respectively). Both Nestin and Ki 67 expression were significantly related to tumor grade (P=0.01 for both) while expression of TP53 was not. (P=0.06). Younger patients’ age and lower Nestin scores significantly correlated with longer patients survival. Conclusions: Higher expression of Nestin and Ki 67 is associated with high grade astrocytomas. The expression scores of Nestin, TP53 and Ki67 are significantly correlated together. Younger patients’ age and lower expression of Nestin have a statistically significant correlation with longer overall survival of patients with astrocytoma.