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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

951
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
951

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Discordance of HER2 Expression and/or Amplification on Repeat Testing.

Timothy P DiPeri1, Kathleen Kong2, Kaushik Varadarajan1

  • 1Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Molecular Cancer Therapeutics
|June 20, 2023
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Summary

HER2 status discordance is common in solid tumors, particularly with HER2 2+ results. Repeat biomarker testing may be valuable before HER2-targeted therapy decisions.

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Area of Science:

  • Oncology
  • Pathology
  • Biomarker Analysis

Background:

  • Accurate HER2 (Human Epidermal growth factor Receptor 2) status is critical for guiding targeted therapy in solid tumors.
  • Discordance in HER2 testing can significantly impact treatment selection and patient outcomes.

Purpose of the Study:

  • To evaluate the rate and patterns of HER2 status discordance in patients with solid tumors undergoing central reevaluation.
  • To assess the impact of biopsy type and intervening therapies on HER2 status concordance.

Main Methods:

  • Central HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) testing were performed on archival or fresh biopsies from 70 patients.
  • Patients had previously identified HER2 expression (IHC) or amplification (FISH/NGS) on local testing.
  • Discordance was analyzed based on local versus central testing results, biopsy type, and treatment history.

Main Results:

  • HER2 status discordance was observed in 30.8% of patients with HER2 overexpression/amplification who underwent new biopsies.
  • Among patients with local HER2 3+ IHC, 30% showed discordance centrally (2+ or lower).
  • Discordance was higher in patients who received HER2-targeted therapy (33.3%) compared to those who did not (23.8%).

Conclusions:

  • Discordance in HER2 status is a significant issue in solid tumors, especially for cases with initially equivocal (2+) results.
  • Repeat central biomarker evaluation is recommended, particularly when considering HER2-targeted therapies, to ensure accurate patient stratification.