Simultaneous expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 receptors in non-small-cell lung carcinomas: correlation with clinical outcome

Lung Cancer. 2007 Aug;57(2):193-200. doi: 10.1016/j.lungcan.2007.03.009. Epub 2007 Apr 17.


The expression of c-erbB receptors was immunohistochemically examined in paraffin embedded specimens from non-small-cell lung carcinomas. A total of 209 patients were enrolled [squamous-cell carcinomas (n=59), adenocarcinomas (n=130), large-cell carcinomas (n=15) and giant-cell carcinomas (n=5)]. The HercepTest kit scoring guidelines were used for the interpretation of positivity. C-erbB-1 was overexpressed in older patients, in squamous-cell carcinomas and in poorly-differentiated tumours, whereas c-erbB-2 overexpression with adenocarcinomas and poorly-differentiated tumours. C-erbB-4 overexpression correlated with advanced disease stage. The c-erbB-1/4 pair was the most commonly overexpressed and significantly correlated with female gender, while the c-erbB-1/2 pair with older age. Response to chemotherapy was significantly reduced in patients with tumours overexpressing c-erbB-1 receptor as well as the c-erbB-1/2 and c-erbB-3/4 receptor pairs. Patients' overall survival was significantly correlated with the co-expression of c-erbB-1 and c-erbB-4 receptors. These findings clearly suggest that specific receptors overexpression or co-overexpression is correlated with patients' disease control rate and outcome. A better understanding of the overexpression of the heterodimerized partners of c-erbB family receptors may provide a useful predictive indicator of response to molecular targeted therapies with c-erbB inhibitors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Proto-Oncogene Proteins / metabolism*
  • Receptor, ErbB-2 / analysis*
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / metabolism
  • Retrospective Studies
  • Survival Analysis


  • Proto-Oncogene Proteins
  • Receptor, ErbB-2