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.