PROGNOSTIC MARKER ANALYSIS IN PEDIATRIC POSTERIOR FOSSA EPENDYMOMAS

Abstract

BACKGROUND: NELL2 expression has been shown to identify patients with posterior fossa ependymomas (PFEp) that exhibit prolonged survivals. We analyzed expression NELL2; KI-67; Tenascin C; CD34; VEGF; and CA IX as well as vascular density against post-operative survival (Progression Free and Overall Survival; PFS, OS) in 31 patients under the age of 22 years. METHODS: PFEp from patients aged 22 years or less were studied. H&E sections were reviewed for grade and vascular status and immunohistochemistry (IHC) was used to determine NELL2; KI-67; Tenascin C; CD34; VEGF; and CA IX status. RESULTS: 3 WHO Grade I, 19 Grade II and 9 Grade III PFEp were studied. Median follow-up time was 9.0 years; median survival was 6.1 years. NELL2 status correlated with PFS (Log Rank P-Value: 0.0220) and exhibited a strong trend towards prolonged OS (Log rank p = 0.0555). Peri-necrotic CAIX localization correlated with PFS (Log rank = 0.0041) and OS (Log rank p = 0.0010) All patients with a CA IX ≤ 5% total area localization were alive at last follow-up. Perinecrotic CAIX staining was also associated with CD34 density (p = .0057) though not with VEGF expression score. MIB-1 labeling index (LI) correlated with OS (p = 0.0185) and PFS (p = 0.0049). MIB-1 LI and perinecrotic CA IX individually correlated with PFS. The effect of perinecrotic CA IX remained when grade was added to a Cox model predicting PFS. There was a significant difference in the distributions of perinecrotic CA IX as stratified by NELL2 expression (Wilcoxon p = 0.0225) with NELL2 negative tumors exhibiting much stronger CA IX expression. CONCLUSIONS: Immunodetection of NELL2 expression was confirmed as a predictive biomarker for PFS in these tumors. This effect is related to the absence of necrosis, low vascular proliferation, low MIB-1 proliferation index, and the absence of CA IX expression. SECONDARY CATEGORY: Pediatrics.