ERBB2 (HER2) is a tyrosine kinase / epidermal growth factor receptor that is overexpressed and mutated in approximately 10-20% of breast cancers. ERBB2 exhibits positive membranous staining in malignant cells, where it promotes cancer cell growth. It is associated with more aggressive tumors. Immunohistochemistry staining of ERBB2 is used alongside the proteins ER (estrogen receptor), PR (progesterone receptor) and Ki-67 to classify different subtypes of breast cancer, and it is a widely used prognostic marker for breast cancer, as levels of ERBB2 expression predict a patient’s response to Herceptin therapy. It is also a relevant marker of poor prognosis for other cancers such as ovarian and gastric cancer, and it is mutated in a small percentage of non-small cell lung cancers. In immunohistochemistry, ERBB2 can show either cytoplasmic or membranous staining, but only membranous staining is relevant for cancer. References: World Journal of Clinical Oncology. 2014 Aug; 5.3; 382-392, PMID: 25114853; PLoS One. 2018; 13(1): e0191972, PMID: 29381731; Pathogenesis. 2015. 2 (3): 1-9, DOI: 10.1016/j.pathog.2015.05.002; World J Gastroenterol. 2016 May 21; 22(19): 4619–4625, PMID: 27217694