Evaluation of Human Epidermal Growth Factor Receptor 2 (HER2) expression in gastric and gastroesophageal junction adenocarcinoma

Introduction: Gastric and gastro-oesophageal junction (GOJ) adenocarcinoma is the fifth most common cancer and fourth leading cause of cancer death globally. HER2 overexpression occurs in 13-22% of gastric and 30% of GOJ adenocarcinoma.
Objective: This was a retrospective study of HER2 (4B5) expression in gastric, oesophageal and GOJ adenocarcinoma reported at a single centre in the United Kingdom. HER2 (4B5) immunohistochemistry (IHC), in situ-hybridization(ISH) status and other pathological data of gastric and GOJ adenocarcinomas reported in both biopsies and resection specimens were collected from January 2014 to December 2022.
Results: A total of 481 patients were included in the study. The median age of patients at the time of surgery was 67.7 years; 68.2% were male. The proportion of patients with of HER2 (4B5) positivity was 13.30% (64/481) . Most HER2 positive tumours were grade 2 (G2) and of intestinal subtype (50%). Of the HER2 positive tumours, most were located at GOJ/Cardia (31; 48.43%), were pT1b (9/64, 39.13%) stage and showed nodal positivity (pN1) (12/64, 52.2%). HER2 assessment had been performed on both biopsies and subsequent resection specimens in 100 patients of which 95 (95%) cases showed concordance of HER2 results. The discordance was mainly due to tumour heterogeneity.
Conclusion: The overall prevalence of HER 2 positivity was 13.30%. HER2 positivity was associated with intestinal subtype rather than diffuse subtype of adenocarcinoma. Tumour heterogeneity was identified as a cause for cases of discordance of HER expression between biopsy and resection specimens.