Overexpression of c-<it>erb</it>B2 is a negative prognostic factor in anaplastic astrocytomas

<p>Abstract</p> <p>The epidermal growth factor receptor (EGFR) family, consisting of four tyrosine kinase receptors, c-<it>erb</it>B1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-<it...

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Bibliographic Details
Main Authors: Gulati Michel, Granli Unn S, Ytterhus Borgny, Gulati Sasha, Lydersen Stian, Torp Sverre H
Format: Article
Language:English
Published: BMC 2010-03-01
Series:Diagnostic Pathology
Online Access:http://www.diagnosticpathology.org/content/5/1/18
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Summary:<p>Abstract</p> <p>The epidermal growth factor receptor (EGFR) family, consisting of four tyrosine kinase receptors, c-<it>erb</it>B1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-<it>erb</it>B1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-<it>erb</it>B1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-<it>erb</it>B2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-<it>erb</it>B3 and c-<it>erb</it>B4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%). After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-<it>erb</it>B2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004). This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-<it>erb</it>B1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-<it>erb</it>B2 overexpression seems to predict aggressive behaviour.</p>
ISSN:1746-1596