A survival guide to HER2 testing in gastric/gastroesophageal junction carcinoma

Human epidermal growth factor receptor 2 (HER2) status determines gastric/gastroesophageal junction (GEJ) adenocarcinomas that benefit from targeted therapy; hence, HER2 testing has become a routine practice. Accurate HER2 testing is fundamental to select eligible patients who will benefit from HER2-targeted treatment. The reported HER2-positive rate in gastric/GEJ cancers ranges from 4.4% to 53.4%, and HER2-positive tumors are considered to have more-aggressive biologic behavior and tumor recurrence. Main modalities of HER2 testing in clinical practice include immunohistochemistry (IHC) for protein expression and in situ hybridization (ISH) for gene amplification. Many technical pitfalls affect the accuracy of HER2 result. Additionally, several issues in HER2 testing are related to the tumor biology, sample selection, interpretation of IHC and ISH results, and confirming HER2 status. Therefore, gastric/GEJ adenocarcinoma-specific HER2 testing protocols have been developed and standardized to minimize the impact of these preanalytical and analytical factors and to enhance reproducibility of HER2 testing results. This review provides up-to-date practical guidance to clinicians on accurate HER2 testing and interpretation of results in gastric/GEJ adenocarcinoma. Human epidermal growth factor receptor 2 (HER2) status determines gastric/gastroesophageal junction (GEJ) adenocarcinomas that benefit from targeted therapy; hence, HER2 testing has become a routine practice. Accurate HER2 testing is fundamental to select eligible patients who will benefit from HER2-targeted treatment. The reported HER2-positive rate in gastric/GEJ cancers ranges from 4.4% to 53.4%, and HER2-positive tumors are considered to have more-aggressive biologic behavior and tumor recurrence. Main modalities of HER2 testing in clinical practice include immunohistochemistry (IHC) for protein expression and in situ hybridization (ISH) for gene amplification. Many technical pitfalls affect the accuracy of HER2 result. Additionally, several issues in HER2 testing are related to the tumor biology, sample selection, interpretation of IHC and ISH results, and confirming HER2 status. Therefore, gastric/GEJ adenocarcinoma-specific HER2 testing protocols have been developed and standardized to minimize the impact of these preanalytical and analytical factors and to enhance reproducibility of HER2 testing results. This review provides up-to-date practical guidance to clinicians on accurate HER2 testing and interpretation of results in gastric/GEJ adenocarcinoma.