Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. A growing body of evidence suggests 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 Ki-67 labeling index are implicated in glioma genesis and therapeutic resistance.
The study included 40 patients (22 male and 18 female) with a mean age of 52.5±11.4 years (range, 26 to 70 y) 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 sex, tumor grade, and patients' survival.
Nestin staining scores ranged between 2 to 9 (mean, 6.30±2.83), whereas those of TP53 ranged between 1 to 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 (ρ=0.34, P=0.03), whereas the correlations of age with Nestin and TP53 scores were not statistically significant (ρ=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 sex (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), whereas expression of TP53 was not (P=0.06). Younger patients' age and lower Nestin scores significantly correlated with longer patients' survival.
Higher expression of Nestin and Ki-67 is associated with high-grade astrocytomas. The expression scores of Nestin, TP53, and Ki-67 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.