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Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1399-408. doi: 10.1158/1055-9965.EPI-09-1213. Epub 2010 May 25.

Grade-specific expression of insulin-like growth factor-binding proteins-2, -3, and -5 in astrocytomas: IGFBP-3 emerges as a strong predictor of survival in patients with newly diagnosed glioblastoma.

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1
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India.

Abstract

BACKGROUND:

Insulin-like growth factor (IGF)-binding protein (IGFBP) isoforms have been implicated in the pathogenesis of human neoplasms including glioma. In view of this, we evaluated the expression of IGFBP isoforms (IGFBP-2, -3, and -5) during malignant progression of astrocytoma and their prognostic significance in glioblastoma.

METHODS:

The expression of IGFBP isoforms was analyzed in diffusely infiltrating astrocytomas by real-time quantitative PCR (n = 203) and immunohistochemistry (n = 256). Statistical methods were used to assess their grade-specific expression pattern and mRNA-protein intercorrelation. Survival analyses were done on a uniformly treated, prospective cohort of adult patients with newly diagnosed glioblastoma (n = 136) by using Cox regression models.

RESULTS:

The mean transcript levels of IGFBP-2 and -3 were significantly higher in glioblastomas (GBM) relative to anaplastic astrocytoma (AA), diffuse astrocytoma (DA), and controls whereas IGFBP-5 mRNA was higher in GBM relative to AA and controls (P < 0.05). By immunohistochemistry, the mean labeling index of all isoforms was significantly higher in GBM compared with AA, DA, and control (P < 0.05). A strong positive correlation was observed between their respective mRNA and protein expressions (P < 0.01). Multivariate analysis revealed IGFBP-3 expression (hazard ratio, 1.021; P = 0.030) and patient age (hazard ratio, 1.027; P = 0.007) to be associated with shorter survival in glioblastoma.

CONCLUSIONS:

This study shows the associations of IGFBP-2, -3, and -5 expression with increasing grades of malignancy in astrocytomas. IGFBP-3 is identified as a novel prognostic glioblastoma biomarker. The strong correlation between their mRNA and protein expression patterns suggests their role in the pathogenesis of these tumors.

IMPACT:

IGFBP isoforms have emerged as biomarkers with diagnostic and prognostic utility in astrocytomas.

PMID:
20501753
DOI:
10.1158/1055-9965.EPI-09-1213
[Indexed for MEDLINE]
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