Her2 low (but not negative): the newest biomarker on the block for gastro-oesophageal adenocarcinoma

In this issue of Journal of Clinical Pathology, Angerilli et al provide a detailed survey of the prevalence and characteristics of HER2 expression by immunohistochemistry (IHC) in gastric and gastro-oesophageal junction carcinoma (GGEJC) from over 1000 cases in Italy.1 They found that the estimate prevalence of HER2 low status in GGEJC was 28.3%. HER2 low status was not associated with stage or PD-L1 IHC or EBER ISH status, and interestingly HER2 low status was present in 27.5% of diffuse type/poorly cohesive carcinomas. The prevalence of HER2 low was higher in biopsies than resections (34.9%) compared with 21.0%.1

This study is in line with prevalence data from another recent study that showed HER2 low prevalence is approximately 21% in patient with inoperable or metastatic gastric carcinoma.2 Trastuzumab for HER2 overexpression/ HER2 amplification was one of the first target therapies for solid tumour, and it was the first targeted therapy for gastric carcinoma, adding 2.7 months to overall survival in a study published 13 years ago.3 More recently, other gastric and pan-cancer targeted therapies have increased the amount of biomarker testing that is routinely performed for inoperable and/or metastatic GGEJC including microsatellite instability/mismatch repair status, BRAF p. V600E mutation status, tumour mutation burden (TMB), PD-L1 IHC, and NTRK and RET gene fusions.

HER2, also known as Erbb2, …

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