Epidermal growth factor receptor, HER-2/neu and related pathways in lung adenocarcinomas with bronchioloalveolar features

Erman M., Grunenwald D., Penault-Llorca F., Grenier J., Besse B., Validire P., ...More

LUNG CANCER, vol.47, no.3, pp.315-323, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 3
  • Publication Date: 2005
  • Doi Number: 10.1016/j.lungcan.2004.08.015
  • Journal Name: LUNG CANCER
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.315-323
  • Hacettepe University Affiliated: No


Lung adenocarcinomas with bronchioalveolar features (ABAF), formerly called bronchioloalveolar cancers (BAC), constitute a distinct clinical, radiological and pathological entity among lung malignancies. Epidermal growth factor receptor (EGFR) and to a less extent, HER-2/neu, are known to be overexpressed in non-small lung cancers, but their exact status in ABAF is not welt-documented. Stimulation of these two receptors results in the initiation of two major cascades, namely phosphatidylinositol 3-kinase (PI-3K) and Ras-dependent pathways. We have therefore studied the expressions of EGFR, HER-2/neu as welt as phosphorylated AKT (pAKT) and phosphorylated extracellular-signal regulated kinase (ERK), which are key molecules in these two pathways, in 15 ABAF patients. EGFR was found to be overexpressed in 9 of 15 patients (60%). HER-2/neu overexpression was detected in 6 of the 14 tumors tested (43%). pAKT and pERK were both found to be positive in 13 of 15 patients (87%) Six of the seven tumors with mucinous pattern were negative for EGFR, while all of the other eight cases were positive (P = 0.001). Mucinous' tumors were also less likely than non-mucinous tumors to overexpress HER-2/neu (17% versus 63%, respectively). These findings suggest that ABAF, particularly those with non-mucinous histology, commonly harbors EGFR and. HER-2/neu overexpression. PI-3K and Ras-dependant pathways that lie downstream are generally activated, even in the absence of EGFR and/or HER-2/neu overexpression. ABAF may be a particularly promising candidate for EGFR-targeted strategies and this possibility merits extensive evaluation in clinical trials. (c) 2004 Elsevier Ireland Ltd. All rights reserved.