Consistent Absence of HER2 Expression, Regardless of HER2 Amplification Status, in Neuroendocrine Carcinomas of the Stomach

Aims: To determine HER2 amplification status and HER2 overexpression status in neuroendocrine carcinomas (NECs) of the stomach.

Methods And Results: We analysed 51 gastric NECs, including 15 pure NECs and 36 NECs associated with adenocarcinoma and/or dysplasia, for HER2 amplification by dual-colour chromogenic in-situ hybridization, and for HER2 expression by immunohistochemistry. HER2 amplification was observed in three NECs (6%) and in seven (19%) cases of adenocarcinoma/dysplasia associated with NEC. Immunohistochemically, all of the NECs, including those showing HER2 amplification, lacked HER2 expression. On the other hand, positive and equivocal HER2 overexpression was observed in three (8%) and six (17%) cases of adenocarcinoma/dysplasia associated with NEC, respectively.

Conclusions: HER2 expression is consistently absent in gastric NECs, regardless of HER2 amplification status or association with HER2-positive adenocarcinoma/dysplasia components. Accordingly, HER2 is unlikely to be a valid therapeutic target in gastric NECs. Also, the absence of HER2 expression in NECs could be one of the causes of intratumoral heterogeneity of HER2 expression in gastric cancers.