Comprehensive assessment of HER2 alteration in a colorectal cancer cohort: from next-generation sequencing to clinical significance

Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic target in colorectal cancer (CRC). Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been used to determine HER2-positive CRCs; however, the clinical utility of next-generation sequencin...

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Bibliographic Details
Published in:Cancer management and research 2019-08, Vol.11, p.7867-7875
Main Authors: Yeh, Yu-Min, Lee, Chun-Hui, Chen, Shang-Hung, Lee, Chung-Ta, Chen, Yi-Lin, Lin, Bo-Wen, Lin, Shao-Chieh, Chan, Ren-Hao, Lee, Jenq-Chang, Shen, Meng-Ru, Lin, Peng-Chan
Format: Article
Language:English
Subjects:
Care and treatment
Colorectal cancer
Epidermal growth factors
Fluorescence
Health aspects
HER2
Immunohistochemistry
Lapatinib
next generation sequencing
Original Research
Pertuzumab
PIK3CA
Surgery
Tumors
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Summary:Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic target in colorectal cancer (CRC). Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been used to determine HER2-positive CRCs; however, the clinical utility of next-generation sequencing (NGS)-based techniques for determining HER2 status in CRC has been limited. Here, we detail our experience regarding the assessment of alterations in a CRC cohort. We prospectively enrolled 73 CRC patients who underwent surgery and received adjuvant oxaliplatin treatment. We then examined alterations using the Oncomine Comprehensive Assay version 1, as well as clinical outcomes, in this cohort. Using the NGS-based assay, copy number gains in 12 of 73 CRCs were determined to range from 2.74 to 92.62. Of these 12 tumors, 6 had high-level copy number gain (92.6, 57.9, 57.0, 52.0, 35.2, and 8.42) and were all defined as HER2-positive CRC using HERACLES Diagnostic Criteria. Nevertheless, other 6 patients with low-level copy number gain (ranging from 2.74 to 3.04) and the remaining 61 patients without increase in copy number were all HER2-negative. Among the 6 HER2-positive CRCs, and mutations were detected in 1 (17%; G13D) and 2 (33.3%; 1 Q546R and 1 H1047R) patients, respectively. Moreover, 2 of the 6 (33.3%) HER2-positive patients had recurrent disease, while one patient had a partial response after anti-HER2 therapy. NGS-based tools could assist in the simultaneous detection of and other genomic alterations in patients with CRC. Only CRCs with high-level copy number gain were HER2-postive by current diagnostic criteria.
ISSN:1179-1322
1179-1322
DOI:10.2147/CMAR.S213247