{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:31:04Z","timestamp":1775197864657,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: 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\u2013pathological variables, metastatic involvement, and overall survival (OS) among advanced gastric cancer patients. Materials and Methods: 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\u2019s Chi-square, Fisher\u2019s exact test, ANOVA, and Kaplan\u2013Meier survival analysis. Results: Significant differences were observed among HER-2 subgroups in pathological subtype (p = 0.006), liver metastasis (p = 0.009), lung metastasis (p = 0.006), and other metastatic sites (p = 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 (p = 0.001) and other metastases (p &lt; 0.001). Median OS for the entire cohort was 9.83 months (95% CI: 8.29\u201311.36). HER-2-positive patients had a significantly longer OS (15.06 months) compared with HER-2-negative patients (8.73 months; p = 0.039). Conclusions: 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.<\/jats:p>","DOI":"10.3390\/medicina61091675","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T16:27:33Z","timestamp":1757953653000},"page":"1675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Effect of HER2 Status on Gastric Cancer Survival and the Clinical Implications of the HER2-Low Definition: A Retrospective Study"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8596-4233","authenticated-orcid":false,"given":"Mehmet","family":"Uzun","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Health Sciences University, Tepecik Training and Research Hospital, 35180 Izmir, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savas","family":"Gokcek","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Necip Faz\u0131l City Hospital, 46050 Kahramanmaras, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-9632","authenticated-orcid":false,"given":"Melis","family":"Kilinc","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Buca Seyfi Demirsoy Training and Research Hospital, 35360 Izmir, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9317-942X","authenticated-orcid":false,"given":"Ferhat","family":"Ekinci","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical Oncology Department, Manisa Celal Bayar University, 45020 Manisa, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-7058","authenticated-orcid":false,"given":"Tugay","family":"Avci","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical Oncology Department, Manisa Celal Bayar University, 45020 Manisa, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4859-7574","authenticated-orcid":false,"given":"Atike Pinar","family":"Erdogan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical Oncology Department, Manisa Celal Bayar University, 45020 Manisa, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif","family":"Atag","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dokuz Eyl\u00fcl University, 35340 Izmir, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9124-6123","authenticated-orcid":false,"given":"Ilkay Tugba","family":"Unek","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dokuz Eyl\u00fcl University, 35340 Izmir, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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