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Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH
DC Field | Value | Language |
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dc.contributor.author | Catenacci, Daniel V. T. | - |
dc.contributor.author | Liao, Wei-Li | - |
dc.contributor.author | Zhao, Lei | - |
dc.contributor.author | Whitcomb, Emma | - |
dc.contributor.author | Henderson, Les | - |
dc.contributor.author | O'Day, Emily | - |
dc.contributor.author | Xu, Peng | - |
dc.contributor.author | Thyparambil, Sheeno | - |
dc.contributor.author | Krizman, David | - |
dc.contributor.author | Bengali, Kathleen | - |
dc.contributor.author | Uzzell, Jamar | - |
dc.contributor.author | Darfler, Marlene | - |
dc.contributor.author | Cecchi, Fabiola | - |
dc.contributor.author | Blackler, Adele | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.contributor.author | Hart, John | - |
dc.contributor.author | Xiao, Shu-Yuan | - |
dc.contributor.author | Lee, Sang Mee | - |
dc.contributor.author | Burrows, Jon | - |
dc.contributor.author | Hembrough, Todd | - |
dc.date.accessioned | 2021-01-31T11:10:29Z | - |
dc.date.available | 2021-01-31T11:10:29Z | - |
dc.date.created | 2018-09-07 | - |
dc.date.issued | 2016-10 | - |
dc.identifier.citation | Gastric Cancer, Vol.19 No.4, pp.1066-1079 | - |
dc.identifier.issn | 1436-3291 | - |
dc.identifier.other | 52044 | - |
dc.identifier.uri | https://hdl.handle.net/10371/173079 | - |
dc.description.abstract | 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. 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.language | 영어 | - |
dc.publisher | Springer Verlag | - |
dc.title | Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1007/s10120-015-0566-0 | - |
dc.citation.journaltitle | Gastric Cancer | - |
dc.identifier.wosid | 000385253600004 | - |
dc.identifier.scopusid | 2-s2.0-84947443812 | - |
dc.citation.endpage | 1079 | - |
dc.citation.number | 4 | - |
dc.citation.startpage | 1066 | - |
dc.citation.volume | 19 | - |
dc.identifier.sci | 000385253600004 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ADVANCED BREAST-CANCER | - |
dc.subject.keywordPlus | ADVANCED GASTRIC-CANCER | - |
dc.subject.keywordPlus | GENE AMPLIFICATION | - |
dc.subject.keywordPlus | INTRATUMORAL HETEROGENEITY | - |
dc.subject.keywordPlus | CLINICOPATHOLOGICAL SIGNIFICANCE | - |
dc.subject.keywordPlus | ESOPHAGEAL ADENOCARCINOMA | - |
dc.subject.keywordPlus | TRASTUZUMAB | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | LAPATINIB | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordAuthor | Her2 expression | - |
dc.subject.keywordAuthor | HER2 (ERBB2) amplification | - |
dc.subject.keywordAuthor | Gastric | - |
dc.subject.keywordAuthor | Esophageal | - |
dc.subject.keywordAuthor | Gastroesophageal adenocarcinoma | - |
dc.subject.keywordAuthor | Stomach cancer | - |
dc.subject.keywordAuthor | SRM-MS | - |
dc.subject.keywordAuthor | Selected reaction monitoring mass spectrometry | - |
dc.subject.keywordAuthor | Companion diagnostic | - |
dc.subject.keywordAuthor | Clinical biomarker assay | - |
dc.subject.keywordAuthor | Multiplex protein expression analysis in FFPE tissue | - |
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