HER2 genomic heterogeneity is a frequent event in gastroesophageal adenocarcinoma and correlates with tumor morphology

Aim: To characterize a cohort of gastro-esophageal adenocarcinomas (GEA) evaluated for HER2 gene amplification using bright field in situ hybridization (ISH) following the 2016 guidelines for GEA and correlating the results with clinico-pathological features. It was also aimed to evaluate the effect of applying the ISH criteria from the 2018 guidelines for breast cancer (BC) in the same GEA cases. Materials and methods: 159 GEA cases collected in a period of 59 months were evaluated for HER2 gene amplification by ISH according to GEA and BC guidelines. All cases were reviewed for histological type, grading and presence of signet ring cells. Results: Most of the cases refereed to ISH were HER2 equivocal (57.9 %) by immunohistochemistry. According to the GEA guideline, 131 cases were HER2-negative (87.3 %) and 19 cases were HER2-positive (12.7 %). According to the BC guideline, 133 cases were HER2-negative (88.7 %) and 17 cases were HER2-positive (11.3 %), being statistically similar to the results obtained with the GEA guideline. HER2 genomic heterogeneity was detected in 31.6 % of the HER2-positive cases, almost exclusively in tubular adenocarcinoma. We observed a significant association between HER2 gene amplification and tubular adenocarcinomas, and absence of signet ring cells. The only case with HER2 gene amplification and presence of signet ring cells was a mixed carcinoma, where the signet ring cells represented the non-amplified component. Conclusions: HER2 positivity rate was similar when applying the GEA or the BC guidelines. We also establish a tight association between morphology and HER2 gene amplification.