Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas

Br J Cancer. 2002 May 6;86(9):1449-56. doi: 10.1038/sj.bjc.6600286.


HER-2/neu gene amplification and cell surface overexpression are important factors in breast cancer for prognosis and prediction of sensitivity to anti-HER-2/neu monoclonal antibody therapy. In lung cancer, the clinical significance of HER-2/neu expression is currently under evaluation. We investigated 238 non-small lung carcinomas for HER-2/neu protein overexpression by immunohistochemistry using the HercepTest. We found 2+ or 3+ overexpression in 39 patients (16%), including 35% in adenocarcinomas and 20% in large cell carcinomas, but only 1% of squamous cell carcinomas. Marked (3+) overexpression was uncommon (4%). The association between protein expression and gene copy number per cell, as determined by fluorescence in situ hybridisation assay, was investigated in 51 of these NSCLC tumours. Twenty-seven tumours (53%) were negative by both tests. Marked (3+) protein expression and gene amplification were present in only 4% of samples. In 11 tumours (21%), gene gain was accompanied by chromosomal aneusomy and did not result in high protein levels while in 7 (14%) the score 2+ was associated with maximum number of signals per cell <9. The prognostic implication of HER-2/neu protein expression was studied in 187 surgically resected tumours. No statistical difference in survival was observed comparing patients with positive (2+/3+) and negative tumours (0/1+), although 3+ patients showed a tendency to shorter survival. The therapeutic implications of protein expression and gene amplification in lung cancer need to be examined in prospective clinical trials.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2 / biosynthesis*
  • Survival Analysis


  • Receptor, ErbB-2