Prognostic value of novel biomarkers in astrocytic brain tumors: nuclear receptor co-regulators AIB1, TIF2, and PELP1 are associated with high tumor grade and worse patient prognosis

J Neurooncol. 2012 Jan;106(1):23-31. doi: 10.1007/s11060-011-0637-y. Epub 2011 Jul 7.

Abstract

Estrogen receptors alpha (ERα) and beta (ERβ) and their co-regulatory proteins are key components of complex signaling networks that specifically regulate the growth and development of various tissues and tumors. Still, their protein expression profiles and possible role in the pathogenesis of astrocytic tumors remain largely unknown. The purpose of the present study is to evaluate the differential protein expression of ΕRα, ERβ, and their co-activators, AIB1, TIF2, and PELP1 in astrocytic tumors of World Health Organization (WHO) grade II-IV, using immunohistochemistry. Potential correlations with clinicopathological parameters and patient prognosis were also explored. ERα protein expression was undetectable while ERβ levels were significantly decreased with progression of tumor grade (P < 0.001). High expression of ERβ was an independent favorable prognostic factor on multivariate analysis (P = 0.003). Expression of AIB1, TIF2, and PELP1 was not correlated with ERβ expression and followed an opposite trend, with increasing levels in high-grade relative to low-grade tumors (P < 0.001). Univariate survival analysis revealed that high AIB1, TIF2, and PELP1 expression was associated with worse prognosis (P = 0.049, P = 0.033, and P = 0.020, respectively). ERβ and ER co-activators AIB1, TIF2, and PELP1 appear to play an important role in the pathogenesis and progression of astrocytic tumors and might have prognostic significance. The mechanisms underlying their involvement in astrocytic tumorigenesis, as well as their utility for prognostic and therapeutic purposes merit further investigation.

MeSH terms

  • Adult
  • Analysis of Variance
  • Astrocytoma / diagnosis
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Co-Repressor Proteins / analysis*
  • Estrogen Receptor beta / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Nuclear Receptor Coactivator 2 / analysis*
  • Nuclear Receptor Coactivator 3 / analysis*
  • Paraffin Embedding
  • Prognosis
  • Survival Analysis
  • Tissue Fixation
  • Transcription Factors / analysis*

Substances

  • Biomarkers, Tumor
  • Co-Repressor Proteins
  • Estrogen Receptor beta
  • NCOA2 protein, human
  • Neoplasm Proteins
  • Nuclear Receptor Coactivator 2
  • PELP1 protein, human
  • Transcription Factors
  • NCOA3 protein, human
  • Nuclear Receptor Coactivator 3