Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites.

25 Background: Determination of HER2 status in advanced gastric cancer (GC) is important in clinical decision making. In the ToGA trial, trastuzumab based therapy demonstrated a significant OS benefit in patients with HER2 positive advanced GC. HER2 discordance in GC primary and its metastases has been long debated. The aim of the study was to evaluate the rate of HER2 discordance and its effect on treatment decisions in advanced GC. Methods: A total of 74 patients with advanced GC were included in the study. Both immunohistochemical staining (IHC) and dual-color silver in situ hybridization (SISH) were performed in all patients to evaluate the HER2 status of the primary lesion and paired metastasis. Results: The assessment of HER2 status with the IHC staining method and SISH revealed a discordance rate of 9.5% and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a HER2 negative status in primary tumor (IHC=0, SISH=negative), the HER2 status was positive for liver metastasis (IHC=2+, SISH=positive). Trastuzumab was added to the chemotherapy regimen. Conclusions: In this study, we found a higher rate of HER2 discordance between primary gastric tumor and metastatic lesions compared to the rates reported in previous studies. Detection of a HER2 positive metastasis with a HER2 negative primary tumor suggests that investigation of HER2 is also required for the metastatic lesion and that trastuzumab could be administered in case of a positive result.