HER2 Testing in Gastric and Gastroesophageal Adenocarcinoma—Review and Update

Adenocarcinomas of the stomach and gastroesophageal junction are commonly encountered by practicing pathologists. In cases of advanced unresectable or metastatic disease, a patient may be a candidate for anti–human epidermal growth factor receptor 2 (HER2) targeted therapy. Eligibility for anti-HER2 therapy is determined by the pathologist, following an algorithm utilizing HER2 immunohistochemistry alone or in combination with chromogenic or fluorescence in situ hybridization. HER2 immunohistochemistry is interpreted using 4-tier scoring criteria that were devised and validated specifically for gastric adenocarcinomas. Here, current guidelines for utilization and interpretation of HER2 immunohistochemistry and in situ hybridization are reviewed. Also included is a discussion of some of the interpretation difficulties and pitfalls that may be encountered in routine pathology practice.