Related Experiment Video

Updated: Dec 2, 2025

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
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Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Published on: December 5, 2017

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HER2 Mutated and Nonmutated Non-small Cell Lung Carcinomas Can Harbor Heterogeneous HER2 Gene Amplification and HER2

Marine Castillon1, Amélie Bourhis1, Isabelle Quintin-Roué1

  • 1Department of Pathology, CHRU Brest.

Applied Immunohistochemistry & Molecular Morphology : AIMM
|November 3, 2020
PubMed

Insights

HER2 alterations in non-small cell lung cancer (NSCLC) show significant heterogeneity in protein expression and gene copy number. This spatial heterogeneity complicates treatment decisions for advanced NSCLC patients receiving anti-HER2 therapies.

Area of Science:

  • Oncology
  • Molecular Pathology
  • Genetics

Background:

  • Molecular profiling is crucial for guiding treatment in advanced non-small cell lung cancer (NSCLC).
  • HER2 alterations (mutation, amplification, protein expression) are emerging therapeutic targets in NSCLC.
  • Discrepant data and tumor heterogeneity pose challenges for treatment selection.

Purpose of the Study:

  • To evaluate HER2 protein expression and gene copy number variations in advanced NSCLC.
  • To investigate HER2 alterations across different tumor areas and samples.
  • To assess the impact of HER2 mutations on protein expression and gene amplification.

Main Methods:

  • Retrospective study of advanced NSCLC patients.
  • Analysis of HER2 protein expression via immunohistochemistry.
  • Assessment of HER2 gene and chromosome 17 copy number variations using fluorescence in situ hybridization (FISH).
  • Comparison between HER2-mutated and HER2-nonmutated NSCLC cohorts.

Main Results:

  • Frequent heterogeneous HER2 protein expression observed in both HER2-mutated and nonmutated NSCLC.
  • No correlation found between HER2 protein expression and HER2 gene copy number variations.
  • HER2 gene amplification occurred in 6 patients, with intra- and inter-sample heterogeneity noted in 3 cases.
  • Spatial heterogeneity of HER2 alterations was evident across tumor samples.

Conclusions:

  • HER2 alterations in NSCLC exhibit significant spatial and inter-sample heterogeneity.
  • This heterogeneity presents a challenge for developing predictive strategies for anti-HER2 therapies.
  • Clinical decision-making for advanced NSCLC requires consideration of HER2 alteration variability.

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