Expression of epidermal growth factor receptor and HER-2 in pediatric embryonal brain tumors.
ABSTRACT Medulloblastomas (MBs), atypical teratoid rhabdoid tumors (AT/RTs) and central nervous system primitive neuroectodermal tumors (PNETs) are aggressive embryonal brain neoplasms in children with overlapping histological features but with different pathogenetic pathways. We set out to evaluate the role of epidermal growth factor receptor (EGFR), HER-2, Ki-67 and p53 in embryonal tumors.
We retrospectively evaluated 36 children with embryonic tumors (27 MBs, 7 AT/RTs and 2 supratentorial PNETs). The immunohistochemical expression of EGFR and HER-2 was correlated to histology, expression of the Ki-67/MIB-1 proliferative index, p53 tumor suppressor oncoprotein and prognosis.
High expression of Ki-67 was observed in all MBs being particularly increased (> 50%) in 8 cases, while p53 protein was detected in 25/27 MBs showing a high expression in 16 cases. EGFR and HER-2 expression was observed in 10/27 and 17/27 MBs, respectively. High Ki-67/MIB-1 and p53 expression was revealed in all AT/RTs and PNETs, while EGFR and HER-2 were detected in 3/7 and 6/7 AT/RTs, respectively. The 5-year progression-free survival and overall survival were 55.5 and 69.2%, respectively. In MBs, the univariate analysis revealed that the Ki-67 index and male gender were both at a significant level related to the survival of the patient. In multivariate analysis, the Ki-67 index was the only independent predictive variable.
The Ki-67 index was identified as a factor with independent prognostic power. EGFR and HER-2 expression is variable in embryonal tumors. HER-2 expression, in a considerable number of MBs and AT/RTs, suggests that HER-2 may be implicated in their pathogenesis representing a potential target for novel therapies.