PMID- 26581548
OWN - NLM
STAT- MEDLINE
DCOM- 20170307
LR  - 20240213
IS  - 1436-3305 (Electronic)
IS  - 1436-3291 (Print)
IS  - 1436-3291 (Linking)
VI  - 19
IP  - 4
DP  - 2016 Oct
TI  - Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: 
      comparison to IHC and FISH.
PG  - 1066-1079
LID - 10.1007/s10120-015-0566-0 [doi]
AB  - BACKGROUND: Trastuzumab has shown a survival benefit in cases of Her2-positive 
      gastroesophageal cancer (GEC). Immunohistochemistry (IHC) and fluorescence in 
      situ hybridization (FISH) currently determine eligibility for trastuzumab-based 
      therapy. However, these low-throughput assays often produce discordant or 
      equivocal results. METHODS: We developed a targeted proteomic assay based on 
      selected reaction monitoring mass spectrometry (SRM-MS) and quantified levels 
      (amol/mug) of Her2-SRM protein in cell lines (n = 27) and GEC tissues (n = 139). 
      We compared Her2-SRM protein expression with IHC/FISH, seeking to determine 
      optimal SRM protein expression cutoffs in order to identify HER2 gene 
      amplification. RESULTS: After demonstrating assay development, precision, and 
      stability, Her2-SRM protein measurement was observed to be highly concordant with 
      the HER2/CEP17 ratio, particularly in a multivariate regression model adjusted 
      for SRM expression of the covariates Met, Egfr, Her3, and HER2 heterogeneity, as 
      well as their interactions (cell lines r (2) = 0.9842; FFPE r (2) = 0.7643). In 
      GEC tissues, Her2-SRM protein was detected at any level in 71.2 % of cases. ROC 
      curves demonstrated that Her2-SRM protein levels have a high specificity (100 %) 
      at an upper-level cutoff of >750 amol/microg and sensitivity of 75 % at a lower-level 
      cutoff of <450 amol/mug for identifying HER2 FISH-amplified tumors. An "equivocal 
      zone" of 450-750 amol/microg of Her2-SRM protein was analogous to IHC2+ but 
      represented fewer cases (9-16 % of cases versus 36-41 %). CONCLUSIONS: Compared 
      to IHC, targeted SRM-Her2 proteomics provided more objective and quantitative 
      Her2 expression with excellent HER2/CEP17 FISH correlation and fewer equivocal 
      cases. Along with its multiplex capability for other relevant oncoproteins, these 
      results demonstrate a refined HER2 protein expression assay for clinical 
      application.
FAU - Catenacci, Daniel V T
AU  - Catenacci DVT
AD  - Department of Medicine, Section of Hematology/Oncology, University of Chicago 
      Medical Center, Chicago, IL, 60637, USA. dcatenac@medicine.bsd.uchicago.edu.
FAU - Liao, Wei-Li
AU  - Liao WL
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
AD  - NantOmics, LLC, Culver City, CA, USA.
FAU - Zhao, Lei
AU  - Zhao L
AD  - Department of Pathology, University of Chicago, Chicago, IL, USA.
FAU - Whitcomb, Emma
AU  - Whitcomb E
AD  - Department of Pathology, University of Chicago, Chicago, IL, USA.
FAU - Henderson, Les
AU  - Henderson L
AD  - Department of Medicine, Section of Hematology/Oncology, University of Chicago 
      Medical Center, Chicago, IL, 60637, USA.
FAU - O'Day, Emily
AU  - O'Day E
AD  - Department of Medicine, Section of Hematology/Oncology, University of Chicago 
      Medical Center, Chicago, IL, 60637, USA.
FAU - Xu, Peng
AU  - Xu P
AD  - Department of Medicine, Section of Hematology/Oncology, University of Chicago 
      Medical Center, Chicago, IL, 60637, USA.
FAU - Thyparambil, Sheeno
AU  - Thyparambil S
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
AD  - NantOmics, LLC, Culver City, CA, USA.
FAU - Krizman, David
AU  - Krizman D
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
AD  - NantOmics, LLC, Culver City, CA, USA.
FAU - Bengali, Kathleen
AU  - Bengali K
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
AD  - NantOmics, LLC, Culver City, CA, USA.
FAU - Uzzell, Jamar
AU  - Uzzell J
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
FAU - Darfler, Marlene
AU  - Darfler M
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
AD  - NantOmics, LLC, Culver City, CA, USA.
FAU - Cecchi, Fabiola
AU  - Cecchi F
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
AD  - NantOmics, LLC, Culver City, CA, USA.
FAU - Blackler, Adele
AU  - Blackler A
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
AD  - NantOmics, LLC, Culver City, CA, USA.
FAU - Bang, Yung-Jue
AU  - Bang YJ
AD  - Seoul National University College of Medicine, Seoul, Korea.
FAU - Hart, John
AU  - Hart J
AD  - Department of Pathology, University of Chicago, Chicago, IL, USA.
FAU - Xiao, Shu-Yuan
AU  - Xiao SY
AD  - Department of Pathology, University of Chicago, Chicago, IL, USA.
FAU - Lee, Sang Mee
AU  - Lee SM
AD  - Department of Public Health Studies, University of Chicago, Chicago, IL, USA.
FAU - Burrows, Jon
AU  - Burrows J
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
FAU - Hembrough, Todd
AU  - Hembrough T
AD  - OncoPlex Diagnostics Inc., Rockville, MD, USA.
AD  - NantOmics, LLC, Culver City, CA, USA.
LA  - eng
GR  - K12 CA139160/CA/NCI NIH HHS/United States
GR  - K23 CA178203/CA/NCI NIH HHS/United States
GR  - P30 CA014599/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
DEP - 20151118
PL  - Japan
TA  - Gastric Cancer
JT  - Gastric cancer : official journal of the International Gastric Cancer Association 
      and the Japanese Gastric Cancer Association
JID - 100886238
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/metabolism
MH  - Gene Amplification
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Proteomics/*methods
MH  - Receptor, ErbB-2/*genetics/*metabolism
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods
MH  - Stomach Neoplasms/*genetics/*metabolism/pathology
PMC - PMC4871781
MID - NIHMS739526
OTO - NOTNLM
OT  - Clinical biomarker assay
OT  - Companion diagnostic
OT  - Esophageal
OT  - Gastric
OT  - Gastroesophageal adenocarcinoma
OT  - HER2 (ERBB2) amplification
OT  - Her2 expression
OT  - Multiplex protein expression analysis in FFPE tissue
OT  - SRM-MS
OT  - Selected reaction monitoring mass spectrometry
OT  - Stomach cancer
EDAT- 2015/11/20 06:00
MHDA- 2017/03/08 06:00
PMCR- 2017/10/01
CRDT- 2015/11/20 06:00
PHST- 2015/05/11 00:00 [received]
PHST- 2015/10/31 00:00 [accepted]
PHST- 2015/11/20 06:00 [entrez]
PHST- 2015/11/20 06:00 [pubmed]
PHST- 2017/03/08 06:00 [medline]
PHST- 2017/10/01 00:00 [pmc-release]
AID - 10.1007/s10120-015-0566-0 [pii]
AID - 10.1007/s10120-015-0566-0 [doi]
PST - ppublish
SO  - Gastric Cancer. 2016 Oct;19(4):1066-1079. doi: 10.1007/s10120-015-0566-0. Epub 
      2015 Nov 18.