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Genomic profiling of primary colorectal adenocarcinomas with HER2 gene (ERBB2) amplification
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Sun Mi Lee1,
Chang Ohk Sung2 |
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1Department of Pathology, Jeju National University Hospital, 2Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center |
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| Her2/neu positivity rates in colorectal cancers are not consistent and controversial, ranging from 2.7% to 47.7%. We assessed the prevalence of HER2 overexpression/amplification in a series of 1046 primary CRC samples revealed by immunohistochemistry and silver in situ hybridization (SISH) and further performed next-generation sequencing (NGS). We have prospectively performed immunohistochemistry for cerbB2 on all surgically resected primary CRCs and detected 242 positive tumors. Tumors with Her2 amplification confirmed by SISH subject to molecular profiling using NGS and were examined substitutions and variations of copy numbers in 392 cancer-related genes. In total, 44 of 1046 primary CRCs were HER2 amplified (4.2%) on SISH and 41 tumors arose from the rectosigmoid colon. Sequence variations of HER2 amplified 44 tumors were observed in TP53, KRAS, APC, SMAD4, PIK3CA, and ERBB2/3. Her2 amplification was found in NGS showing a mean copy number of 13 ranging from 2 to 39 copy numbers. Her2 amplification was identified in 4.2% of 1046 primary CRCs and predominantly left colon. Main oncogenic mutations including TP53, KRAS, APC, and PIK3CA were observed in Her2 amplified 44 CRCs. These findings suggest that anti-HER2 therapy is beneficial for 4-5% of patients with CRC, particularly left colon. NGS-based tools could assist in the simultaneous detection of HER2 amplification in patients with CRC. |
Index Term 1: HER2 amplified colorectal cancer
Index Term 2: next-generation sequencing
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