Clinical Significance:
Recently established guidelines from the American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and/or the American Society of Clinical Oncology (ASCP) recommend testing for all newly diagnosed non-small cell, non-squamous lung carcinomas or such metastatic lung carcinomas that have not had a primary resection available for testing. ERBB2 (HER2) mutations are an emerging biomarker in NSCLC patient tumors, with the most common being exon 20 insertions (ERBB2 p.774_775insAYVM and ERBB2 p.776_776G>VC).  These mutations have been associated with responsiveness to HER-tyrosine kinase inhibitors (TKIs) and anti-HER2 therapies.

https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf

Reference:
Gandhi L, Bahleda R, Tolaney SM, et al. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. J Clin Oncol. 2014;32(2):68-75

Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine in patients with HER2 mutant lung cancers: Results from a phase II basket trial.  J Clin Oncol 2018;36:2532-2537.

Specimen Requirements and Collection:
Formalin-fixed tissue containing a sufficient amount of tumor (generally at least several mm of tumor tissue submitted in the tissue block)

Methodology:
DNA isolation and extraction, library prep, and next-generation sequencing (NGS)

Forms:
Molecular pathology requisition form

Transport:
Send formalin-fixed, paraffin-embedded (FFPE) tissue and cell block containing tumor at room temperature.  Also acceptable 10-unstained, 4-5 micron slides with 1 post H&E.  Please include a surgical pathology report

Unacceptable specimen:
Specimens fixed in alternative fixatives or metal fixatives (ex. B-plus).  Decalcified specimens.

Reference Range:
ERBB2 (HER2) mutation not detected = negative result
ERBB2 (HER2) mutation detected = positive result

CPT codes:
88381, 81403, G0452

Test reported:
Results are reported within 7-10 days