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Comparative analysis of the EGFR, HER2, c-MYC, and MET variations in colorectal cancer determined by three different measures: gene copy number gain, amplification status and the 2013 ASCO/CAP guideline criterion for HER2 testing of breast cancer

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Authors
Kwak, Yoonjin; Yun, Sumi; Nam, Soo Kyung; Seo, An Na; Lee, Kyu Sang; Shin, Eun; Oh, Heung-Kwon; Kim, Duck Woo; Kang, Sung Bum; Kim, Woo Ho; Lee, Hye Seung
Issue Date
2017-08-01
Publisher
BioMed Central
Citation
Journal of Translational Medicine, 15(1):167
Keywords
Gene copy number variationEGFRHER2c-MYCMETColorectal cancer
Description
Abbreviations
GCN: gene copy number; CRC: colorectal cancer; EGFR: human epidermal growth factor receptor; HER2: human epidermal growth receptor 2; SISH: silver in situ hybridization; PFS: progression-free survival; OS: overall survival; TMA: tissue microarray; ASCO/CAP: American Society of Clinical Oncology/College
of American Pathologists; MSI: microsatellite instability.
Abstract
Abstract

Background
The purpose of this study was to explore gene copy number (GCN) variation of EGFR, HER2, c-MYC, and MET in patients with primary colorectal cancer (CRC).

Methods
Dual-colour silver-enhanced in situ hybridization was performed in tissue samples of 334 primary CRC patients. The amplification status (GCN ratio ≥2) and GCN gain (average GCN ≥4) data for the EGFR, HER2, c-MYC and MET genes were obtained. GCN variation was also assessed by the criterion of the 2013 ASCO/CAP guidelines for HER2 testing.

Results
Amplification of EGFR, HER2, c-MYC and MET was detected in 8 (2.4%), 20 (6.0%), 29 (8.7%), and 14 (4.2%) patients, respectively. Of 66 patients with at least one amplified gene, five exhibited co-amplification of genes studied (HER2-MET co-amplification: two patients; HER2-c-MYC co-amplification: two patients; EGFR-c-MYC co-amplification: one patient). There were 109 patients with GCN gains of one or more genes (EGFR: 11/334, HER2: 29/334, c-MYC; 60/334, MET: 48/334) and 32.1% (35/109) had multiple GCN gains. When each GCN was assessed by the criterion of the ASCO/CAP 2013 guideline for HER2 testing, 116 people showed positive or equivocal results for one or more genes. The cumulative amplification status had no association with patients’ outcome. However, the cumulative results of the GCN gain and GCN status determined according to the ASCO/CAP guideline had a significant prognostic correlation in the univariate analysis (P values of 0.006 and 0.022, respectively). In the multivariate analysis, GCN gain and GCN status were independent prognostic factors (P values of 0.010 and 0.017, respectively).

Conclusions
In this study, we evaluated GCN variation of four genes in a large sample of Korean CRC patients. The amplification status was not related to patient outcome. However, the GCN gain and GCN status according to the ASCO/CAP 2013 guideline were independent prognostic factors.
ISSN
1479-5876
Language
English
URI
http://hdl.handle.net/10371/138305
DOI
https://doi.org/10.1186/s12967-017-1265-x
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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