Frequent overexpression of ErbB--receptor family members in brain metastases of non-small cell lung cancer patients

APMIS. 2013 Dec;121(12):1144-52. doi: 10.1111/apm.12063. Epub 2013 Jun 12.

Abstract

The ErbB receptor family has been implicated in brain metastases (BM) formation in various cancer types and specific targeted therapies are available. We investigated the overexpression of EGFR, HER2 and HER3 in BM of non-small cell lung cancer (NSCLC) patients to get a better insight on pathobiology of BM and potential drugable targets. We performed immunohistochemical analysis of EGFR, HER2 and HER3 on tissue microarrays of 131 NSCLC-BM. Fifty-one of 131 (38.9%) specimens were considered as positive for EGFR overexpression, 12/131 (9.2%) for HER2 and 27/131 (20.6%) for HER3 respectively. Sixty-nine of 131 (52.7%) of the cases showed overexpression of at least one marker. Four of 131 (3.1%) were positive for all three markers. Strong correlation was observed between HER2 and HER3 overexpression (p = 0.009; Chi-square test after Bonferroni-Holmes correction). No statistically significant correlation of EGFR, HER2 or HER3 overexpression with clinico-pathological parameters including overall survival times was observed. We observed overexpression of ErbB receptor family members, which represent established therapeutic targets in various primary tumours, in approximately half of NSCLC-BM. Further studies should investigate the role of the ErbB pathway in development of and as a therapeutic target in BM of NSCLC patients.

Keywords: Brain metastases; EGFR; HER2; HER3; lung cancer; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain / pathology
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Non-Small-Cell Lung / therapy
  • ErbB Receptors / biosynthesis*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-3 / biosynthesis*
  • Tissue Array Analysis

Substances

  • EGFR protein, human
  • ERBB2 protein, human
  • ERBB3 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3