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

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


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).


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).


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.

Abbreviations used in this paper:GBM = glioblastoma multiforme; GFAP = glial fibrillary acidic protein; IDH1 = isocitrate dehydrogenase 1; KPS = Karnofsky Performance Scale; NFP = neurofilament protein; PFS = progression-free survival; RPA = recursive partitioning analysis; RTOG = Radiation Therapy Oncology Group; TMZ = temozolomide.

Article Information

Address correspondence to: Johan Pallud, M.D., Service de Neurochirurgie, Hôpital Sainte-Anne, 1 Rue Cabanis, 75674 Paris cedex 14, France. email:

Please include this information when citing this paper: published online June 22, 2012; DOI: 10.3171/2012.5.JNS111670.

© AANS, except where prohibited by US copyright law.



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    Neuroimages (A and B) and photomicrographs (C–G) of GBMs in the study. A: Axial postcontrast T1-weighted FLAIR sequences showing NFP-negative GBMs. In a left parietal NFP-negative GBM (left column), the contrast-enhanced area invades the subventricular zone but does not involve the cortex. In a right parietal NFP-negative GBM (center column) and in a bifrontal NFP-negative GBM (right column), the contrast-enhanced area invades the subventricular zone and the corpus callosum, but does not involve the cortex. B: Axial T2-weighted FLAIR sequences showing NFP-positive GBMs. In 2 right temporal NFP-positive GBMs (left and center columns), the contrast-enhanced area invades the cortex but does not involve the subventricular zone. Note the contrast-enhanced dura mater surrounding a contrast-enhancing area, corresponding to leptomeningeal tumor infiltration. In a right frontal NFP-positive GBM (right column), the contrast-enhanced area extends from the cortex to the subventricular zone but does not involve the corpus callosum. C–G: Images showing classic histological features of a GBM with pseudopalisading necrosis (C), endothelial proliferation, and densely packed astrocytic tumoral cells (D). This tumor exhibited a double immunophenotype with a strong and diffuse expression of GFAP (E) and a neuronal NFP immunoexpression (F and G). Note that individual NFP-positive, mitotically active neoplastic cells are heterogeneously found within the tumoral tissue. Hemalum-phloxine (C and D), GFAP (E), and NFP (F and G). Original magnification × 400.

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    Graphs of Kaplan-Meier estimates of overall survival and PFS according to NFP expression status and oncological treatment. A: Overall survival and PFS in the entire series of 302 supratentorial primary GBMs. B: Overall survival and PFS according to NFP expression. The hazard ratio (HR) for death among patients harboring an NFP-positive GBM, as compared with those harboring an NFP-negative GBM, was 0.54 (95% CI 0.40–0.74; p < 0.0001). The HR for death or disease progression among patients harboring an NFP-positive GBM, as compared with those harboring an NFP-negative GBM, was 0.71 (95% CI 0.53–0.96; p = 0.02). C: Overall survival and PFS according to NFP expression in the subgroup of patients (n = 150) treated with radiotherapy combined with chemotherapy (TMZ). The HR for death among patients harboring an NFP-positive GBM, as compared with those harboring an NFP-negative GBM, was 0.510 (95% CI 0.344–0.755; p = 0.001). The HR for death or disease progression among patients harboring an NFP-positive GBM, as compared with those harboring an NFP-negative GBM, was 0.781 (95% CI 0.534–1.142; p = 0.202).



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