The clinicopathologic values of the molecules associated with the main pathogenesis of the glioblastoma

Abstract

Glioblastoma (GBM) is a malignant CNS neoplasm. The prognosis of GBM may be influenced by the molecules of p53/MDM2/p14ARF, RB/p16INK4a, and the EGFR/PTEN/protein kinase B (PKB)/phosphoinositide 3-kinase (PI3K) pathways. We studied the expression status of specific molecular markers in GBMs by immunohistochemistry (IHC) and FISH in correlation with the clinical outcomes. The positivity of EGFR FISH and those of EGFR IHC by pharmDx and Zymed antibodies were 64.9%, 73.5%, and 43.4%, respectively. EGFR pharmDx antibody was more sensitive but less specific than EGFR Zymed antibody. p53 overexpression, MDM2 expression, p16 loss, PTEN loss, PKB and PI3K expression were found in 48.2%, 26.5%, 56.6%, 21.4%, 15.7% and 6.0%, respectively. EGFR IHC and FISH significantly, although not completely, correlated and EGFR and p53 immunoexpression also showed positive correlation. On multivariate survival studies, old age (≥ 40 yrs) and bilaterality were independent unfavorable prognosis factors ( p < 0.05). Stratified by age, resectability and tumor size < 5 cm were favorable survival factors in young (40 < yrs) and old age groups (≥ 40 yrs), respectively. Furthermore, the patients with supratentorial tumor lived longer than the patients with infratentorial tumor ( p < 0.05). Longer survival (survival length, ≥ 3 years) was statistically less frequent in the patients in the EGFR FISH-positive group ( p = 0.031).