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Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH

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dc.contributor.authorCatenacci, Daniel V. T.-
dc.contributor.authorLiao, Wei-Li-
dc.contributor.authorZhao, Lei-
dc.contributor.authorWhitcomb, Emma-
dc.contributor.authorHenderson, Les-
dc.contributor.authorO'Day, Emily-
dc.contributor.authorXu, Peng-
dc.contributor.authorThyparambil, Sheeno-
dc.contributor.authorKrizman, David-
dc.contributor.authorBengali, Kathleen-
dc.contributor.authorUzzell, Jamar-
dc.contributor.authorDarfler, Marlene-
dc.contributor.authorCecchi, Fabiola-
dc.contributor.authorBlackler, Adele-
dc.contributor.authorBang, Yung-Jue-
dc.contributor.authorHart, John-
dc.contributor.authorXiao, Shu-Yuan-
dc.contributor.authorLee, Sang Mee-
dc.contributor.authorBurrows, Jon-
dc.contributor.authorHembrough, Todd-
dc.date.accessioned2021-01-31T11:10:29Z-
dc.date.available2021-01-31T11:10:29Z-
dc.date.issued2016-10-
dc.identifier.citationGastric Cancer, Vol.19 No.4, pp.1066-1079-
dc.identifier.issn1436-3291-
dc.identifier.other52044-
dc.identifier.urihttps://hdl.handle.net/10371/173079-
dc.description.abstractTrastuzumab 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. We developed a targeted proteomic assay based on selected reaction monitoring mass spectrometry (SRM-MS) and quantified levels (amol/mu g) 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. 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/A mu g and sensitivity of 75 % at a lower-level cutoff of < 450 amol/mu g for identifying HER2 FISH-amplified tumors. An "equivocal zone" of 450-750 amol/A mu g of Her2-SRM protein was analogous to IHC2+ but represented fewer cases (9-16 % of cases versus 36-41 %). 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.-
dc.subjectHer2 expression-
dc.subjectHER2 (ERBB2) amplification-
dc.subjectGastric-
dc.subjectEsophageal-
dc.subjectGastroesophageal adenocarcinoma-
dc.subjectStomach cancer-
dc.subjectSRM-MS-
dc.subjectSelected reaction monitoring mass spectrometry-
dc.subjectCompanion diagnostic-
dc.subjectClinical biomarker assay-
dc.subjectMultiplex protein expression analysis in FFPE tissue-
dc.titleMass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH-
dc.typeArticle-
dc.contributor.AlternativeAuthor방영주-
dc.identifier.doi10.1007/s10120-015-0566-0-
dc.citation.journaltitleGastric Cancer-
dc.identifier.scopusid2-s2.0-84947443812-
dc.citation.endpage1079-
dc.citation.number4-
dc.citation.startpage1066-
dc.citation.volume19-
dc.identifier.urlhttps://link.springer.com/article/10.1007%2Fs10120-015-0566-0-
dc.identifier.rimsid52044-
dc.identifier.sci000385253600004-
dc.contributor.affiliatedAuthorBang, Yung-Jue-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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