HER2 testing in gastric cancer: An update

Abstract

Human epidermal growth factor receptor 2 (HER2) overexpression is increasingly recognized as a frequent molecular abnormality in gastric and gastroesophageal cancer. With the recent introduction of HER2 molecular targeted therapy for patients with advanced gastric cancer, determination of HER2 status is crucial in order to select patients who may benefit from this treatment. This paper provides an update on our knowledge of HER2 in gastric and gastroesophageal cancer, including the prognostic relevance of HER2, the key differences between HER2 protein expression interpretation in breast and gastric cancer, the detection methods and the immunohistochemistry scoring system.

Keywords: Gastric cancer; Human epidermal growth factor receptor 2 testing; Immunohistochemistry; Scoring system; Trastuzumab.

Figure 1

Human epidermal growth factor receptor 2 testing algorithm. HER2: Human epidermal growth factor receptor 2; IHC: Immunohistochemistry; FISH: Fluorescent in situ hybridization; CEP17: Chromosome 17.

Figure 2

Human epidermal growth factor receptor 2 expression in gastric and breast tumors. A: A HER2-positive (3+) case of gastric adenocarcinoma; the cytoplasmic membranous immunostaining is incomplete and predominantly basolateral (× 400); B: A HER2-positive (3+) case of invasive ductal carcinoma of the breast; the cytoplasmic membranous staining is fully circumferential (× 400). HER2: Human epidermal growth factor receptor 2.

Figure 3

Representative image of the intratumoral heterogeneity of HER2 expression. Arrows indicate areas with strong continuous membranous staining (score 3+) and arrowheads indicate negative areas (score 0) (× 100). HER2: Human epidermal growth factor receptor 2.

Figure 4

Human epidermal growth factor receptor 2 protein expression in gastric and gastroesophageal tumors. A: A negative (0) case; B: A negative (+1) case; C: An equivocal (2+) case; D: A positive (3+) case. HER2: Human epidermal growth factor receptor 2.