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

Clinical article

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  • 1 Departments of Neurosurgery,
  • 2 Neuroradiology, and
  • 3 Neuropathology, Sainte-Anne Hospital, Paris;
  • 4 University Paris Descartes, Paris;
  • 5 Biostatistics and Epidemiology Unit, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France;
  • 6 Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona;
  • 7 Department of Radiation Oncology and Physics, Institut Gustave Roussy, Villejuif; and
  • 8 Department of Oncology and Radiotherapy, Tenon Hospital, Paris, France
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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.

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.

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Contributor Notes

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

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

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