Lack of prognostic implications of HER-2/neu abnormalities in 345 stage I non-small cell carcinomas (NSCLC) and 207 stage I-III neuroendocrine tumours (NET) of the lung

Int J Cancer. 2005 Jan 1;113(1):101-8. doi: 10.1002/ijc.20542.


HER-2/neu oncogene activation by either gene amplification and/or protein overexpression has been documented in several human malignancies. Irrespective of protein overexpression, HER-2/neu gene amplification is rare in lung cancer and studies on its prevalence and clinicopathological implications in early stage non-small cell lung cancer (NCSLC) and neuroendocrine tumours (NET) of the lung are lacking. We evaluated HER-2/neu abnormalities in 345 Stage I NSCLC and 207 Stage I-III NET of the lung of all the diverse histological types, by using immunohistochemistry and fluorescent in situ hybridization in selected cases. Overall, HER-2/neu immunoreactivity was detected in 23% of 345 NSCLC and in 7% of 207 NET. Gene amplification was seen in only 7 (7.4%) of the immunoreactive tumours, with high-level amplification (HER-2/neu gene to chromosome 17 ratio > 4.0) in 3 adenocarcinomas, 1 squamous-cell carcinoma and 1 large-cell neuroendocrine carcinoma (LCNEC), and low-level amplification (HER-2/neu gene to chromosome 17 ratio from 2.0 to 4.0) in 1 squamous-cell carcinoma and 1 LCNEC. None of tested carcinoids and SCLC showed gene amplification. All but 1 gene amplified case exhibited 2+ or 3+ membrane labeling. No relationship was found between gene amplification or protein overexpression and patients' survival or other clinicopathological variables. HER-2/neu gene amplification and protein overexpression are not closely correlated in lung carcinomas and do not bear any prognostic implication. Among neuroendocrine tumours, LCNEC show a slightly higher prevalence of either HER-2/neu gene amplification or protein overexpression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 17
  • Female
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic
  • Genes, erbB-2*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies
  • Up-Regulation


  • Receptor, ErbB-2