PMID- 33077919
OWN - NLM
STAT- MEDLINE
DCOM- 20211103
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 34
IP  - 3
DP  - 2021 Mar
TI  - Detection of ERBB2 amplification in uterine serous carcinoma by next-generation 
      sequencing: an approach highly concordant with standard assays.
PG  - 603-612
LID - 10.1038/s41379-020-00695-5 [doi]
AB  - Uterine serous carcinoma is an aggressive subtype of endometrial cancer that 
      accounts for fewer than 10% of endometrial carcinomas but is responsible for 
      about half of deaths. A subset of cases has HER2 overexpression secondary to 
      ERBB2 gene amplification, and these patients may benefit from anti-HER2 
      therapies, such as trastuzumab. HER2 protein overexpression is currently assessed 
      by immunohistochemistry (IHC) and ERBB2 gene amplification by fluorescence in 
      situ hybridization (FISH). Targeted next-generation sequencing (NGS) is 
      increasingly used to routinely identify predictive and prognostic molecular 
      abnormalities in endometrial carcinoma. To investigate the ability of a targeted 
      NGS panel to detect ERBB2 amplification, we identified cases of uterine serous 
      carcinoma (n = 93) and compared HER2 expression by IHC and copy number assessed 
      by FISH with copy number status assessed by NGS. ERBB2 copy number status using a 
      combination of IHC and FISH was interpreted using the 2018 ASCO/CAP guidelines 
      for breast carcinoma. ERBB2 amplification by NGS was determined by the relative 
      number of reads mapping to ERBB2 in tumor DNA compared to control nonneoplastic 
      DNA. Cases with copy number >/=6 were considered amplified and copy number <6 were 
      non-amplified. By IHC, 70 specimens were classified as negative (0 or 1+), 19 
      were classified as equivocal (2+), and 4 were classified as positive (3+). Using 
      combined IHC/FISH, ERBB2 amplification was observed in 8 of 93 cases (9%). NGS 
      identified the same 8 cases with copy number >/=6; all 85 others had copy number 
      <6. In this series, NGS had 100% concordance with combined IHC/FISH in 
      identifying ERBB2 amplification. NGS is highly accurate in detecting ERBB2 
      amplification in uterine serous carcinoma and provides an alternative to 
      measurement by IHC and FISH.
FAU - Robinson, Carrie L
AU  - Robinson CL
AD  - Naval Medical Center San Diego, San Diego, CA, USA.
FAU - Harrison, Beth T
AU  - Harrison BT
AUID- ORCID: 0000-0002-8341-2961
AD  - Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and 
      Women's Hospital, Boston, MA, USA.
FAU - Ligon, Azra H
AU  - Ligon AH
AD  - Department of Pathology, Division of Clinical Cytogenetics, Brigham and Women's 
      Hospital, Boston, MA, USA.
FAU - Dong, Fei
AU  - Dong F
AUID- ORCID: 0000-0003-3769-0247
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
FAU - Maffeis, Valeria
AU  - Maffeis V
AD  - Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, 
      University of Padova, Padova, Italy.
FAU - Matulonis, Ursula
AU  - Matulonis U
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Nucci, Marisa R
AU  - Nucci MR
AD  - Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and 
      Women's Hospital, Boston, MA, USA.
FAU - Kolin, David L
AU  - Kolin DL
AUID- ORCID: 0000-0002-7631-6525
AD  - Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and 
      Women's Hospital, Boston, MA, USA. dkolin@bwh.harvard.edu.
LA  - eng
GR  - UL1 TR002541/TR/NCATS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201019
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  - Biomarkers, Tumor/*genetics
MH  - Carcinoma/*genetics/pathology
MH  - DNA Copy Number Variations
MH  - Endometrial Neoplasms/*genetics/pathology
MH  - Female
MH  - *Gene Amplification
MH  - Gene Dosage
MH  - *High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Neoplasms, Cystic, Mucinous, and Serous/*genetics/pathology
MH  - Predictive Value of Tests
MH  - Receptor, ErbB-2/*genetics
MH  - Reproducibility of Results
MH  - Retrospective Studies
EDAT- 2020/10/21 06:00
MHDA- 2021/11/04 06:00
CRDT- 2020/10/20 06:23
PHST- 2020/05/08 00:00 [received]
PHST- 2020/09/23 00:00 [accepted]
PHST- 2020/09/23 00:00 [revised]
PHST- 2020/10/21 06:00 [pubmed]
PHST- 2021/11/04 06:00 [medline]
PHST- 2020/10/20 06:23 [entrez]
AID - S0893-3952(22)00660-3 [pii]
AID - 10.1038/s41379-020-00695-5 [doi]
PST - ppublish
SO  - Mod Pathol. 2021 Mar;34(3):603-612. doi: 10.1038/s41379-020-00695-5. Epub 2020 
      Oct 19.