Journal
MOLECULAR ONCOLOGY
Volume 10, Issue 1, Pages 138-147Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.molonc.2015.09.002
Keywords
Breast cancer; HER2; Mass spectrometry; Trastuzumab; Immunohistochemistry; In situ hybridization
Categories
Funding
- Tumor Biomarkers Collaboration - Banco Bilbao Vizcaya Argentaria (BBVA) Foundation
- ICREA Funding Source: Custom
- NATIONAL CANCER INSTITUTE [P30CA008748] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Introduction: Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti-HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will respond to anti-HER2 treatments. Methods: Using selected reaction monitoring mass spectrometry (SRM-MS), we quantified HER2 protein levels in formalin-fixed, paraffin-embedded (FFPE) tissue samples that had been classified as HER2 0, 1+, 2+ or 3+ by immunohistochemistry (IHC). Receiver operator curve (ROC) analysis was conducted to obtain optimal HER2 protein expression thresholds predictive of HER2 status (by standard IHC or in situ hybridization [ISH]) and of survival benefit after anti-HER2 therapy. Results: Absolute HER2 amol/mu g levels were significantly correlated with both HER2 IHC and amplification status by ISH (p < 0.0001). A HER2 threshold of 740 amol/mu g showed an agreement rate of 94% with IHC and ISH standard HER2 testing (p < 0.0001). Discordant cases (SRM-MS-negative/ISH-positive) showed a characteristic amplification pattern known as double minutes. HER2 levels >2200 amol/mu g were significantly associated with longer disease-free survival (DFS) and overall survival (OS) in an adjuvant setting and with longer OS in a metastatic setting. Conclusion: Quantitative HER2 measurement by SRM-MS is superior to IHC and ISH in predicting outcome after treatment with anti-HER2 therapy. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available