Expression of pERK and pAKT in pediatric high grade astrocytomas: Correlation with YKL40 and prognostic significance

The Ras signaling pathway, consisting of mitogen‐activated protein kinase (MAPK) and PI3K/AKT signaling, is a prominent oncogenic pathways in adult diffuse gliomas, but few studies have evaluated such pathways in pediatric malignant gliomas. We investigated by immunohistochemistry MAPK and AKT signaling in a series of 28 pediatric high‐grade gliomas (WHO grade III and IV). We sought a possible association of phospho‐ERK (p‐ERK) and phospho‐AKT (p‐AKT) with expression of other proteins involved in the Ras pathway, that is, YKL40, epidermal growth factor receptor (EGFR), EGFR vIII and c‐Met. Moreover we correlated the expression of p‐ERK and p‐AKT with prognosis. No cases showed expression for c‐Met and EGFR, and only one case was positive for EGFR vIII. YKL‐40 protein was expressed in 43% of cases. We detected expression of p‐ERK and p‐AKT in 61% and 57%, respectively, of pediatric high grade gliomas. Statistical analysis comparing the two groups in term of high and low p‐ERK and p‐AKT expression showed a trend toward worse overall survival in patients with high expression of p‐AKT. The activation of ERK and AKT suggest a possible role of this protein in inducing activation of the Ras signaling pathway in pediatric high‐grade gliomas. Moreover high levels of p‐AKT are associated with worse overall survival.