HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies

Abstract

Human epidermal growth factor receptor-2 (HER2)-expression gastro-oesophageal adenocarcinomas (GEA) gained interest as an important target for therapy with trastuzumab. In the current review, we focused the current knowledge on HER2 status in dysplastic and neoplastic gastric conditions, analyzing the methodological procedures to identify HER2 expression/amplification, as well as the proposed scoring recommendations. One of the most relevant questions to evaluate the useful impact of HER2 status on therapeutic choice in GEAs is represented by the significant heterogeneity of HER2 protein and gene expression that may affect the targeted treatment selection. Future development of biotechnology will continue to evolve in order to offer more powerful detection systems for the assessment of HER2 status. Finally, liquid biopsy as well as mutation/amplification of several additional genes may furnish an early detection of secondary HER2 resistance mechanisms in GEAs with a better monitoring of the treatment response.

Keywords: dysplasia; gastric cancer; human epidermal growth factor receptor 2 (HER2); immunohistochemistry; liquid biopsy; neoplastic heterogeneity.

Figure 1

In intestinal-type primary gastric cancer (GC), the heterogeneous 3+ score was present in neoplastic glands either in bioptic ((A), 200×) or in surgical specimens, showing immunoreactive elements in direct contact with negative ones ((B), 240×) (immunohistochemistry, Mayer’s hemalum counterstain).