Neuronal immunoexpression and a distinct subtype of adult primary supratentorial glioblastoma with a better prognosis.
OBJECTIVE
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.
Department of Neurosurgery, Sainte-Anne Hospital, Paris, France. johanpallud@hotmail.com
Johan
J
Pallud
Edouard
E
Dezamis
Etienne
E
Audureau
Bertrand
B
Devaux
Raphaëlle
R
Souillard-Scemama
Nader
N
Sanai
Philippe
P
Page
Frédéric
F
Beuvon
Maria
M
Koziak
Catherine
C
Oppenheim
Frédéric
F
Dhermain
Michel
M
Schlienger
Jean-François
JF
Meder
François-Xavier
FX
Roux
Pascale
P
Varlet
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003131:Combined Modality Therapy; D004358:Drug Therapy; D005260:Female; D005909:Glioblastoma / Q000145:classification* / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D019635:Neurosurgical Procedures; D011379:Prognosis; D011878:Radiotherapy; D012189:Retrospective Studies; D015173:Supratentorial Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000628:therapy; D015996:Survival Rate
D014408:Biomarkers, Tumor; D016900:Neurofilament Proteins