ERBB2 mutation analysis is performed by next-generation sequencing of all coding exons of the ERBB2 gene (also called HER2). This test is not designed to detect HER2 amplifications; please see instead HER2 FISH.
ERBB2 (also known as HER2) gene function may be impaired by point mutations and small insertion/deletion mutations detectable by next-generation sequencing. Such mutations are distinct from HER2 gene amplifications which are frequent in breast and gastroesophageal cancers. ERBB2 mutations are detected at low frequency (generally <=5%) in various solid tumors including breast, lung, biliary, small and large intestine, cervical, gastric, and urinary tract. Frequency of mutations in non-small cell lung cancer (NSCLC) is approximately 1-3%. Tumors with ERBB2 mutation may respond to ERBB2 small molecule inhibitors and antibodies.
- FFPE tissue: Paraffin block is preferred. Alternatively, send 1 H&E slide plus 5-10 unstained slides cut at 5 or more microns. Please use positively-charged slides and 10% NBF fixative. Do not use zinc fixatives.
Use cold pack for transport, making sure cold pack is not in direct contact with specimen.
- Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: Results from a phase II basket trial. J Clin Oncol. 2018;36(24):2532-2537.
- Li BT, Ross DS, Aisner DL, et al. HER2 amplification and HER2 mutation are distinct molecular targets in lung cancers. J Thorac Oncol. 2016;11(3):414-9.
- ERBB2 tissue distribution page. COSMIC website. https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ERBB2#tissue. Accessed December 28, 2018.