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Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

Sasha Gulati1, Borgny Ytterhus, Unn S Granli

  • 1Department of Neurosurgery, St Olavs University Hospital, Trondheim, Norway. sashagulati@hotmail.com

Diagnostic Pathology
|March 25, 2010
PubMed

Insights

Epidermal growth factor receptor (EGFR) family proteins are overexpressed in anaplastic astrocytomas, with c-erbB2 overexpression indicating a poor prognosis. This study confirms EGFR

Area of Science:

  • Molecular oncology
  • Cancer biology
  • Neuro-oncology

Background:

  • The epidermal growth factor receptor (EGFR) family, comprising c-erbB1-4 tyrosine kinases, plays a role in gliomagenesis.
  • Understanding the expression and amplification of EGFR family members is crucial for anaplastic astrocytoma pathogenesis.

Purpose of the Study:

  • To investigate EGFR gene amplification and c-erbB1-4 receptor protein expression in human anaplastic astrocytomas.
  • To determine the prognostic significance of EGFR family protein expression in these tumors.

Main Methods:

  • Immunohistochemistry was used to assess c-erbB1-4 receptor protein expression in 31 formalin-fixed, paraffin-embedded anaplastic astrocytoma tissues.
  • Fluorescence in situ hybridization (FISH) was employed to study EGFR gene amplification.
  • Cox multiple regression analysis was performed to evaluate prognostic factors.

Main Results:

  • High rates of positive immunostaining were observed for EGFR (97%), c-erbB2 (45-100% depending on antibody), c-erbB3 (97%), and c-erbB4 (74%).
  • EGFR gene amplification was detected in 29% of the tumors.
  • Overexpression of c-erbB2, detected by clone CB11, was a significant predictor of poor overall survival (P = 0.004).

Conclusions:

  • Immunohistochemistry is a feasible method for assessing receptor protein expression in astrocytomas.
  • Synchronous overexpression of c-erbB1-4 proteins suggests their involvement in anaplastic astrocytoma pathogenesis.
  • c-erbB2 overexpression is a potential biomarker for aggressive behavior in anaplastic astrocytomas.

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