Neuronal immunoexpression and a distinct subtype of adult primary supratentorial glioblastoma with a better prognosis

Abstract

Object: In this study, the authors address whether neurofilament protein (NFP) expression can be used as an independent prognostic factor in primary glioblastoma multiformes (GBMs).

Methods: Three hundred and two consecutive adult patients with newly diagnosed supratentorial primary GBMs were analyzed (January 2000-August 2008). Detailed data regarding clinical, imaging, and pathological findings, oncological treatments, and outcomes were recorded. Neurofilament protein immunoexpression served to identify NFP-positive tumor cells (normal entrapped neurons and mature ganglion-like cells excluded).

Results: Neurofilament-positive cells were identified in 177 GBMs (58.6%). Patients with NFP-positive GBMs were younger (p < 0.0001), and their GBMs presented with more temporal lobe tumor localization (p = 0.029) and more cortical involvement (p = 0.0003). Neurofilament-negative GBMs presented with more ventricular contact (p < 0.0001) and more tumor midline crossing (p = 0.03). Median overall survival and progression-free survival (PFS) were 13.0 and 7.6 months, respectively, for NFP-positive GBMs, and 7.0 and 5.1 months, respectively, for NFP-negative GBMs. Multivariate analysis revealed NFP immunoexpression, tumor midline crossing, complete resection, and radiotherapy combined with chemotherapy as independent factors associated with overall survival. Neurofilament protein-positive immunoexpression was associated with longer overall survival (hazard ratio [HR] 0.54, 95% CI 0.40-0.74; p < 0.0001) and longer PFS (HR 0.71, 95% CI 0.53-0.96; p = 0.02).

Conclusions: Neurofilament protein-positive immunoexpression represents a strong, therapeutically independent prognostic factor for primary supratentorial GBM clinical outcome among adult patients. Neurofilament protein-GBM's unique pathological features are not only associated with distinct clinical and anatomical behavior, but are also predictive of overall patient survival and PFS. Neurofilament protein immunoexpression may help identify a distinct subgroup of primary GBMs with a favorable prognosis, which should be considered in the design of future targeted therapies.