PMID- 33001186
OWN - NLM
STAT- MEDLINE
DCOM- 20210524
LR  - 20210524
IS  - 1530-8561 (Electronic)
IS  - 0009-9147 (Linking)
VI  - 66
IP  - 10
DP  - 2020 Oct 1
TI  - Clinical Application of Multiple Reaction Monitoring-Mass Spectrometry to Human 
      Epidermal Growth Factor Receptor 2 Measurements as a Potential Diagnostic Tool 
      for Breast Cancer Therapy.
PG  - 1339-1348
LID - 10.1093/clinchem/hvaa178 [doi]
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is often 
      overexpressed in breast cancer and correlates with a worse prognosis. Thus, the 
      accurate detection of HER2 is crucial for providing the appropriate measures for 
      patients. However, the current techniques used to detect HER2 status, 
      immunohistochemistry and fluorescence in situ hybridization (FISH), have 
      limitations. Specifically, FISH, which is mandatory for arbitrating 2+ cases, is 
      time-consuming and costly. To address this shortcoming, we established a multiple 
      reaction monitoring-mass spectrometry (MRM-MS) assay that improves on existing 
      methods for differentiating HER2 status. METHODS: We quantified HER2 expression 
      levels in 210 breast cancer formalin-fixed paraffin-embedded (FFPE) tissue 
      samples by MRM-MS. We aimed to improve the accuracy and precision of HER2 
      quantification by simplifying the sample preparation through predicting the 
      number of FFPE slides required to ensure an adequate amount of protein and using 
      the expression levels of an epithelial cell-specific protein as a normalization 
      factor when measuring HER2 expression levels. RESULTS: To assess the correlation 
      between MRM-MS and IHC/FISH data, HER2 quantitative data from MRM-MS were divided 
      by the expression levels of junctional adhesion molecule A, an epithelial 
      cell-specific protein, prior to statistical analysis. The normalized HER2 amounts 
      distinguished between HER2 2+/FISH-negative and 2+/FISH-positive groups (AUROC = 
      0.908), which could not be differentiated by IHC. In addition, all HER2 status 
      were discriminated by MRM-MS. CONCLUSIONS: This MRM-MS assay yields more accurate 
      HER2 expression levels relative to immunohistochemistry and should help to guide 
      clinicians toward the proper treatment for breast cancer patients, based on their 
      HER2 expression.
CI  - (c) American Association for Clinical Chemistry 2020. All rights reserved. For 
      permissions, please email: journals.permissions@oup.com.
FAU - Do, Misol
AU  - Do M
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Kim, Hyunsoo
AU  - Kim H
AD  - Department of Biomedical Engineering, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Yeo, Injoon
AU  - Yeo I
AD  - Department of Biomedical Engineering, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Lee, Jihyeon
AU  - Lee J
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Park, In Ae
AU  - Park IA
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Ryu, Han Suk
AU  - Ryu HS
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Kim, Youngsoo
AU  - Kim Y
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
AD  - Department of Biomedical Engineering, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Chem
JT  - Clinical chemistry
JID - 9421549
RN  - 0 (Biomarkers, Tumor)
RN  - 1HG84L3525 (Formaldehyde)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Biomarkers, Tumor/*analysis
MH  - Breast Neoplasms/*diagnosis
MH  - Female
MH  - Formaldehyde/chemistry
MH  - Humans
MH  - Mass Spectrometry/*methods
MH  - Middle Aged
MH  - Paraffin Embedding
MH  - Receptor, ErbB-2/*analysis
MH  - Tissue Fixation
OTO - NOTNLM
OT  - breast cancer
OT  - formalin-fixed paraffin-embedded (FFPE)
OT  - human epidermal growth factor receptor 2 (HER2)
OT  - multiple reaction monitoring-mass spectrometry (MRM-MS)
OT  - targeted proteomics
EDAT- 2020/10/02 06:00
MHDA- 2021/05/25 06:00
CRDT- 2020/10/01 12:14
PHST- 2020/03/03 00:00 [received]
PHST- 2020/07/13 00:00 [accepted]
PHST- 2020/10/01 12:14 [entrez]
PHST- 2020/10/02 06:00 [pubmed]
PHST- 2021/05/25 06:00 [medline]
AID - 5904418 [pii]
AID - 10.1093/clinchem/hvaa178 [doi]
PST - ppublish
SO  - Clin Chem. 2020 Oct 1;66(10):1339-1348. doi: 10.1093/clinchem/hvaa178.