Overexpression of c-erb B2 is a negative prognostic factor in anaplastic astrocytomas

Abstract

The epidermal growth factor receptor (EGFR) family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 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-erbB1-4 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-erbB2 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-erbB3 and c-erbB4 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-erbB2 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-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.

miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL

“…However, the role of LATS2 in glioblastoma tumorigenesis and the underlying molecular mechanisms had remained largely unknown. ERBB2, a known proto-oncogene, is located at the long arm of human chromosome 17 (17q12) [39], and overexpression of ERBB2 is a negative prognostic factor in anaplastic astrocytomas [40]. However, the relationship between miRNA and ERBB2 in GBM is remained largely unknown.…”

Expression and clinical value of EGFR in human meningiomas

“…In the present study, nearly all tumors expressed both domains (99.5% for the ECD, 100% for ICD), even though the internal domain had an overall higher intensity. High levels of ICD positivity have also been observed in high-grade astrocytomas and non-small cell lung cancer (Gulati et al, 2010; Mascaux et al, 2011; Torp et al, 2007), although negative immunoreactivity has also been reported (Wickremesekera, Hovens & Kaye, 2010). Concerning the ECD, most studies have shown high expression (Andersson et al, 2004; Baxter et al, 2014; Camby et al, 1997; Diedrich et al, 1995; Guillaudeau et al, 2012), whereas some have recorded lower positivity (Jones et al, 1990).…”

Overexpression of CXCR4 promotes invasion and migration of non‑small cell lung cancer via EGFR and MMP‑9

“…In turn, previous studies demonstrated that vascular endothelial growth factor increases the CXCR4 expression of endothelial cells, increases CXCL12 endothelial cell activity, promotes the generation of blood and lymphatic vessels and induces tumor cells to specific organs (11,12). Epidermal growth factor receptor (EGFR), a type of transmembrane glycoprotein, exists on the cell surface and is encoded by the proto-oncogene c-erb-B1 (13). Ligand-mediated EGFR signaling, such as the RAS/extracellular-signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/protein kinase B pathways, regulates various cellular processes, including cell survival, death, growth, proliferation and motility (14).…”