The prognostic value of nestin expression in newly diagnosed glioblastoma: report from the Radiation Therapy Oncology Group.
BACKGROUND
Nestin is an intermediate filament protein that has been implicated in early stages of neuronal lineage commitment. Based on the heterogeneous expression of nestin in GBM and its potential to serve as a marker for a dedifferentiated, and perhaps more aggressive phenotype, the Radiation Therapy Oncology Group (RTOG) sought to determine the prognostic value of nestin expression in newly diagnosed GBM patients treated on prior prospective RTOG clinical trials.


METHODS
Tissue microarrays were prepared from 156 patients enrolled in these trials. These specimens were stained using a mouse monoclonal antibody specific for nestin and expression was measured by computerized quantitative image analysis using the Ariol SL-50 system. The parameters measured included both staining intensity and the relative area of expression within a specimen. This resulted into 3 categories: low, intermediate, and high nestin expression, which was then correlated with clinical outcome.


RESULTS
A total of 153 of the 156 samples were evaluable for this study. There were no statistically significant differences between pretreatment patient characteristics and nestin expression. There was no statistically significant difference in either overall survival or progression-free survival (PFS) demonstrated, although a trend in decreased PFS was observed with high nestin expression (p = 0.06).


CONCLUSIONS
Although the correlation of nestin expression and histologic grade in glioma is of considerable interest, the presented data does not support its prognostic value in newly diagnosed GBM. Further studies evaluating nestin expression may be more informative when studied in lower grade glioma, in the context of markers more specific to tumor stem cells, and using more recent specimens from patients treated with temozolomide in conjunction with radiation.
Chinnaiyan
Prakash
P
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. prakash.chinnaiyan@moffitt.org
Wang
Meihua
M
Rojiani
Amyn M
AM
Tofilon
Philip J
PJ
Chakravarti
Arnab
A
Ang
K Kian
KK
Zhang
Hua-Zhong
HZ
Hammond
Elizabeth
E
Curran
Walter
W
Mehta
Minesh P
MP
D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D019070:Cell Lineage; D003131:Combined Modality Therapy / Q000379:methods; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D064231:Nestin; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D012107:Research Design; D000077204:Temozolomide; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D003606:Dacarbazine; D000077204:Temozolomide