Prognostic significance of human epidermal growth factor receptor 2 in gastric signet-ring cell carcinoma: Neoadjuvant chemotherapy interaction study

BACKGROUNDThe prognostic significance of human epidermal growth factor receptor 2 (HER2) in gastric signet-ring cell carcinoma (GSRCC) remains poorly defined, and the clinical relevance of HER2-low expression in this histological subtype is unclear. AIMTo evaluate the prognostic impact of HER2 status and its interaction with neoadjuvant chemotherapy (NAC) in patients with GSRCC. METHODSPatients with GSRCC who were treated at the study center were retrospectively enrolled.HER2 status was classified as negative [immunohistochemistry (IHC) 0], low (IHC 1+ or 2+/in situ hybridization negative), or positive (IHC 3+ or 2+/in situ hybridization positive).Overall survival (OS) was assessed using Kaplan-Meier curves and Cox proportional hazards regression models.The interaction between HER2 status and NAC was assessed using an HER2 × NAC interaction term.Propensity score matching was also performed to reduce potential treatmentselection bias in the NAC-related analyses. RESULTSHER2 positivity was identified in 26 patients, whereas 523 were HER2-negative and 584 had HER2-low tumors.HER2 positivity was independently associated with poorer OS [hazard ratio (HR) = 1.943, 95%CI: 1.035-3.648;P = 0.039].A significant interaction between HER2 status and NAC was observed in the overall cohort (P for interaction < 0.001).Before matching, NAC was associated with poorer OS in the HER2-negative and HER2-low subgroups (HR = 3.54 and HR = 2.94, respectively).After 1:1 propensity score matching, 82 patients who received NAC were matched to 82 patients who underwent upfront surgery.NAC remained associated with poorer 4 / 35 OS in the matched cohort (HR = 1.89, 95%CI: 1.22-2.93;P = 0.005), and similar associations were observed in the HER2-negative and HER2-low subgroups. CONCLUSIONHER2 positivity is independently associated with poor OS, whereas HER2-low expression is not.The significant interaction suggests that patients with HER2negative or HER2-low GSRCC may not benefit from NAC.