PMID- 32161378
OWN - NLM
STAT- MEDLINE
DCOM- 20210708
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 33
IP  - 8
DP  - 2020 Aug
TI  - Integrated genomic characterization of ERBB2/HER2 alterations in invasive breast 
      carcinoma: a focus on unusual FISH groups.
PG  - 1546-1556
LID - 10.1038/s41379-020-0504-5 [doi]
AB  - In patients with invasive breast cancer, fluorescence in situ hybridization 
      (FISH) testing for HER2 typically demonstrates the clear presence or lack of 
      ERBB2 (HER2) amplification (i.e., groups 1 or 5). However, a small subset of 
      patients can present with unusual HER2 FISH patterns (groups 2-4), resulting in 
      diagnostic confusion. To provide clarity, the 2018 CAP/ASCO HER2 testing 
      guideline recommends additional testing using HER2 immunohistochemistry (IHC) for 
      determining the final HER2 status. Despite this effort, the genomic correlates of 
      unusual HER2 FISH groups remain poorly understood. Here, we used droplet digital 
      PCR (ddPCR) and targeted next-generation sequencing (NGS) to characterize the 
      genomic features of both usual and unusual HER2 FISH groups. In this study, 51 
      clinical samples were selected to represent FISH groups 1-5. Furthermore, group 1 
      was subdivided into two groups, with groups 1A and 1B corresponding to cases with 
      HER2 signals/cell >/=6.0 and 4-6, respectively. Overall, our findings revealed a 
      wide range of copy number alterations in HER2 across the different FISH groups. 
      As expected, groups 1A and 5 showed the clear presence and lack of HER2 copy 
      number gain, respectively, as measured by ddPCR and NGS. In contrast, group 1B 
      and other uncommon FISH groups (groups 2-4) were characterized by a broader range 
      of HER2 copy levels with only a few select cases showing high-level gain. 
      Notably, these cases with increased HER2 copy levels also showed HER2 
      overexpression by IHC, thus highlighting the correlation between HER2 copy number 
      and HER2 protein expression. Given the concordance between the genomic and 
      protein results, our findings suggest that HER2 IHC may inform HER2 copy number 
      status in patients with unusual FISH patterns. Hence, our results support the 
      current recommendation for using IHC to resolve HER2 status in FISH groups 2-4.
FAU - Yang, Soo-Ryum
AU  - Yang SR
AUID- ORCID: 0000-0002-1051-502X
AD  - Department of Pathology, School of Medicine, Stanford University, Stanford, CA, 
      USA.
FAU - Bouhlal, Yosr
AU  - Bouhlal Y
AD  - TOMA Biosciences, Holland, MI, USA.
FAU - De La Vega, Francisco M
AU  - De La Vega FM
AD  - TOMA Biosciences, Holland, MI, USA.
AD  - Department of Biomedical Data Science, School of Medicine, Stanford University, 
      Stanford, CA, USA.
FAU - Ballard, Morgan
AU  - Ballard M
AD  - Department of Pathology, School of Medicine, Stanford University, Stanford, CA, 
      USA.
FAU - Kuo, Calvin J
AU  - Kuo CJ
AD  - Department of Medicine, School of Medicine, Stanford University, Stanford, CA, 
      USA.
FAU - Vilborg, Anna
AU  - Vilborg A
AD  - TOMA Biosciences, Holland, MI, USA.
FAU - Jensen, Greg
AU  - Jensen G
AD  - TOMA Biosciences, Holland, MI, USA.
FAU - Allison, Kimberly
AU  - Allison K
AD  - Department of Pathology, School of Medicine, Stanford University, Stanford, CA, 
      USA. allisonk@stanford.edu.
LA  - eng
PT  - Journal Article
DEP - 20200311
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*analysis/genetics
MH  - Breast Neoplasms/*genetics
MH  - DNA Copy Number Variations
MH  - Female
MH  - High-Throughput Nucleotide Sequencing/methods
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Middle Aged
MH  - Polymerase Chain Reaction/methods
MH  - Receptor, ErbB-2/analysis/*genetics
MH  - Sequence Analysis, DNA/methods
EDAT- 2020/03/13 06:00
MHDA- 2021/07/09 06:00
CRDT- 2020/03/13 06:00
PHST- 2019/08/19 00:00 [received]
PHST- 2020/01/30 00:00 [accepted]
PHST- 2020/01/11 00:00 [revised]
PHST- 2020/03/13 06:00 [pubmed]
PHST- 2021/07/09 06:00 [medline]
PHST- 2020/03/13 06:00 [entrez]
AID - S0893-3952(22)00797-9 [pii]
AID - 10.1038/s41379-020-0504-5 [doi]
PST - ppublish
SO  - Mod Pathol. 2020 Aug;33(8):1546-1556. doi: 10.1038/s41379-020-0504-5. Epub 2020 
      Mar 11.