PMID- 34963694
OWN - NLM
STAT- MEDLINE
DCOM- 20220707
LR  - 20230724
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 35
IP  - 7
DP  - 2022 Jul
TI  - ERBB2 amplification status in 67 salivary duct carcinomas assessed by 
      immunohistochemistry, fluorescence in situ hybridization, and targeted exome 
      sequencing.
PG  - 895-902
LID - 10.1038/s41379-021-00999-0 [doi]
AB  - Salivary duct carcinoma (SDC) is an aggressive salivary gland malignancy with 
      poor survival. Approximately 30% SDC harbor HER2 amplification and response to 
      trastuzumab has been reported. However, a systematic approach for HER2 status 
      assessment in this tumor type has not been established. A total of 67 tumor 
      samples were evaluated for HER2 protein overexpression or ERBB2 gene 
      amplification using at least 2 methods: immunohistochemistry (IHC), fluorescence 
      in situ hybridization (FISH), and/or targeted exome next-generation sequencing 
      (NGS). NGS assessed ERBB2 copy number fold change (FC) and total copy number 
      (TCN). HER2 status was first determined by IHC/FISH according to the 2018 
      ASCO/CAP breast cancer guidelines. FISH results, the "gold standard", were 
      compared with the NGS results. All (15/15) IHC positive, 35% (6/17) equivocal, 
      and no (0/19) IHC negative SDC were HER2 amplified by FISH. HER2 FISH signal/cell 
      showed a good correlation with FC (Spearman correlation: 0.708, R(2): 0.501, 
      p < 0.0001) and TCN (Spearman correlation: 0.763, R(2): 0.582, p < 0.0001). 
      Receiver operating characteristics curve estimation showed an area under curve 
      (AUC) of 0.975 for ERBB2 FC. FC cutoff of >/=1.8 corresponded to an accuracy of 
      95.2% for ERBB2 amplification (Youden's index: 0.84, sensitivity: 89.47%, 
      specificity: 100%). FC < 1.3 could be reliably classified as ERBB2 not amplified 
      and FC >/= 1.3 and <1.8 as equivocal. TCN estimation showed AUC of 0.981. TCN 
      cutoff of >6.0 corresponded to an accuracy of 92% for HER2 amplification 
      (Youden's index: 0.81, sensitivity: 81.2%, specificity: 100%). TCN < 4 could be 
      reliably classified as ERBB2 not amplified and TCN >/= 4.0 and </=6.0 as equivocal. 
      FC and TCN were binarized with respective cutoffs of >/=1.8 and >/=6.0 and the 
      proportion of agreement with FISH were 95% and 92%, respectively. The assessment 
      of ERBB2 copy number by NGS is accurate and reliable with FC or TCN nearly 
      equivalent to FISH in identifying HER2 amplified SDC.
CI  - (c) 2021. The Author(s), under exclusive licence to United States & Canadian 
      Academy of Pathology.
FAU - Ferguson, Donna C
AU  - Ferguson DC
AD  - Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      10065, USA.
FAU - Momeni Boroujeni, Amir
AU  - Momeni Boroujeni A
AUID- ORCID: 0000-0002-7714-370X
AD  - Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      10065, USA.
FAU - Zheng, Tao
AU  - Zheng T
AD  - Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      10065, USA.
FAU - Mohanty, Abhinita S
AU  - Mohanty AS
AD  - Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      10065, USA.
FAU - Ho, Alan L
AU  - Ho AL
AD  - Departments of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 
      10065, USA.
FAU - Arcila, Maria E
AU  - Arcila ME
AD  - Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      10065, USA.
FAU - Ross, Dara S
AU  - Ross DS
AD  - Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      10065, USA.
FAU - Dogan, Snjezana
AU  - Dogan S
AUID- ORCID: 0000-0002-4905-8946
AD  - Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      10065, USA. dogans@mskcc.org.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20211228
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, Ductal/genetics
MH  - Exome
MH  - Gene Amplification
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Receptor, ErbB-2/genetics/metabolism
MH  - Salivary Ducts/metabolism/pathology
MH  - *Salivary Gland Neoplasms/genetics
PMC - PMC10363285
MID - NIHMS1912381
COIS- Disclosure of Potential Competing Interests No conflict of interests exists for 
      all contributory authors. Disclosure Statement: No competing financial interests 
      exist for all contributory authors. Research reported in this publication was 
      supported by the Memorial Sloan Kettering Cancer Center Support Grant of the 
      National Institutes of Health/National Cancer Institute under award number 
      P30CA008748. The content is solely the responsibility of the authors and does not 
      necessarily represent the official views of the National Institutes of Health.
EDAT- 2021/12/30 06:00
MHDA- 2022/07/08 06:00
PMCR- 2023/07/23
CRDT- 2021/12/29 05:34
PHST- 2021/08/31 00:00 [received]
PHST- 2021/12/08 00:00 [accepted]
PHST- 2021/12/06 00:00 [revised]
PHST- 2021/12/30 06:00 [pubmed]
PHST- 2022/07/08 06:00 [medline]
PHST- 2021/12/29 05:34 [entrez]
PHST- 2023/07/23 00:00 [pmc-release]
AID - S0893-3952(22)00078-3 [pii]
AID - 10.1038/s41379-021-00999-0 [doi]
PST - ppublish
SO  - Mod Pathol. 2022 Jul;35(7):895-902. doi: 10.1038/s41379-021-00999-0. Epub 2021 
      Dec 28.