UMMS Affiliation

Department of Molecular, Cell and Cancer Biology

Date

2-21-2017

Document Type

Article Postprint

Disciplines

Cancer Biology | Computational Biology | Genomics | Neoplasms | Pathology

Abstract

HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2-positive because of HER2 IHC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P < 0.001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment.

Rights and Permissions

Citation: Hum Pathol. 2017 Feb 21. pii: S0046-8177(17)30051-5. doi: 10.1016/j.humpath.2017.02.004. [Epub ahead of print] Link to article on publisher's site

DOI of Published Version

10.1016/j.humpath.2017.02.004

Comments

Full list of authors omitted for brevity. For full list see article.

Related Resources

Link to Article in PubMed

Keywords

HER2, colorectal cancer, next-generation sequencing, comprehensive genomic sequencing, immunohistochemistry, fluorescence in situ hybridization

Journal Title

Human pathology

PubMed ID

28235632

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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