E. Strong (ed.). Gastric cancer. Principles and practice. Springer (2015)
The HER2 oncogene encodes a transmembrane tyrosine kinase receptor that belongs to the epidermal growth factor receptor (EGFR) family. This family is composed of EGFR/HER1, HER2/ neu, HER3, and HER4, which play essential roles in promoting cell growth, migration, differentiation, proliferation, and survival. Each receptor has an extracellular domain, lipophilic transmembrane domain, and intracellular tyrosine kinase domain. Activation of the kinase occurs with ligand binding leading to receptor dimerization. HER2 is ligand independent and may be activated due to mutations in HER2 or receptor overexpression .
The rates of HER2 amplification or overexpression in esophagogastric cancers vary with the primary location of the cancer. The rates are highest in GEJ or stomach cardia tumors, with 20–30% HER2 positivity . In the mid and distal stomach 15–20% are HER2-positive, and only 5–6% of diffuse or signet ring cell type tumors are positive for the mutation [5, 6].
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