The Effect of HER2 Status on Gastric Cancer Survival and the Clinical Implications of the HER2-Low Definition: A Retrospective Study

<i>Background and Objectives</i>: HER-2 expression plays a critical role in the biological behavior and treatment of gastric cancer. With the emergence of HER-2-targeted therapies, classification into negative, low, and positive groups has gained clinical importance. The present study focused on assessing the link between HER-2 status and clinical-pathological variables, metastatic involvement, and overall survival (OS) among advanced gastric cancer patients. <i>Materials and Methods</i>: A total of 300 patients with advanced gastric adenocarcinoma were retrospectively analyzed. The mean age of the 300 patients included in the study was 61.8 years, and 70% of them were male. Based on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), patients were classified as HER-2-negative (IHC 0), HER-2-low (IHC 1+ or 2+/FISH-negative), or HER-2-positive (IHC 3+ or 2+/FISH-positive). Clinicopathological variables, metastatic sites, and OS were compared among groups using Pearson's Chi-square, Fisher's exact test, ANOVA, and Kaplan-Meier survival analysis. <i>Results</i>: Significant differences were observed among HER-2 subgroups in pathological subtype (<i>p</i> = 0.006), liver metastasis (<i>p</i> = 0.009), lung metastasis (<i>p</i> = 0.006), and other metastatic sites (<i>p</i> = 0.001). HER-2-positive patients demonstrated higher rates of adenocarcinoma histology and increased liver and lung metastases. In female patients, HER-2 status was significantly associated with lung (<i>p</i> = 0.001) and other metastases (<i>p</i> < 0.001). Median OS for the entire cohort was 9.83 months (95% CI: 8.29-11.36). HER-2-positive patients had a significantly longer OS (15.06 months) compared with HER-2-negative patients (8.73 months; <i>p</i> = 0.039). <i>Conclusions</i>: HER-2 status is an important predictor of metastatic behavior and survival in advanced gastric cancer. HER-2-positive patients display distinct metastatic patterns and improved outcomes, supporting the value of HER-2-targeted therapies. The HER-2-low group may represent a biologically and clinically relevant intermediate subtype requiring further investigation.