| Title |
Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH
|
|---|---|
| Published in |
Gastric Cancer, November 2015
|
| DOI | 10.1007/s10120-015-0566-0 |
| Pubmed ID | |
| Authors |
Daniel V. T. Catenacci, Wei-Li Liao, Lei Zhao, Emma Whitcomb, Les Henderson, Emily O’Day, Peng Xu, Sheeno Thyparambil, David Krizman, Kathleen Bengali, Jamar Uzzell, Marlene Darfler, Fabiola Cecchi, Adele Blackler, Yung-Jue Bang, John Hart, Shu-Yuan Xiao, Sang Mee Lee, Jon Burrows, Todd Hembrough |
| 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/μg) 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/µg and sensitivity of 75 % at a lower-level cutoff of <450 amol/μg for identifying HER2 FISH-amplified tumors. An "equivocal zone" of 450-750 amol/µg 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. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 50% |
| Comoros | 1 | 25% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 50% |
| Practitioners (doctors, other healthcare professionals) | 1 | 25% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 32 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 5 | 16% |
| Professor > Associate Professor | 4 | 13% |
| Student > Postgraduate | 3 | 9% |
| Student > Ph. D. Student | 3 | 9% |
| Student > Bachelor | 2 | 6% |
| Other | 5 | 16% |
| Unknown | 10 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 28% |
| Biochemistry, Genetics and Molecular Biology | 5 | 16% |
| Agricultural and Biological Sciences | 2 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Nursing and Health Professions | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 12 | 38% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 April 2021.
All research outputs
#13,959,398
of 22,833,393 outputs
Outputs from Gastric Cancer
#267
of 597 outputs
Outputs of similar age
#195,364
of 386,425 outputs
Outputs of similar age from Gastric Cancer
#3
of 11 outputs
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