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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.
J Transl Med. 2017 08 01; 15(1):167.JT

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.

Authors+Show Affiliations

Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, Republic of Korea.Department of Diagnostic Pathology, Samkwang Medical Laboratories, Seoul, Republic of Korea.Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, Republic of Korea.Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea.Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, Republic of Korea.Department of Pathology, Veterans Health Service Medical Center, Seoul, Republic of Korea.Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, Republic of Korea. hye2@snu.ac.kr.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

28764718

Citation

Kwak, Yoonjin, et al. "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." Journal of Translational Medicine, vol. 15, no. 1, 2017, p. 167.
Kwak Y, Yun S, Nam SK, et al. 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. J Transl Med. 2017;15(1):167.
Kwak, Y., Yun, S., Nam, S. K., Seo, A. N., Lee, K. S., Shin, E., Oh, H. K., Kim, D. W., Kang, S. B., Kim, W. H., & Lee, H. S. (2017). 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. Journal of Translational Medicine, 15(1), 167. https://doi.org/10.1186/s12967-017-1265-x
Kwak Y, et al. 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. J Transl Med. 2017 08 1;15(1):167. PubMed PMID: 28764718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kwak,Yoonjin, AU - Yun,Sumi, AU - Nam,Soo Kyung, AU - Seo,An Na, AU - Lee,Kyu Sang, AU - Shin,Eun, AU - Oh,Heung-Kwon, AU - Kim,Duck Woo, AU - Kang,Sung Bum, AU - Kim,Woo Ho, AU - Lee,Hye Seung, Y1 - 2017/08/01/ PY - 2017/01/11/received PY - 2017/07/19/accepted PY - 2017/8/3/entrez PY - 2017/8/3/pubmed PY - 2018/5/31/medline KW - Colorectal cancer KW - EGFR KW - Gene copy number variation KW - HER2 KW - MET KW - c-MYC SP - 167 EP - 167 JF - Journal of translational medicine JO - J Transl Med VL - 15 IS - 1 N2 - 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. SN - 1479-5876 UR - https://www.unboundmedicine.com/medline/citation/28764718/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_ L2 - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1265-x DB - PRIME DP - Unbound Medicine ER -