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The amplified expression of Human epidermal growth factor receptor\u20102 (HER\u20102) and microsatellite stable (MSI) status serve as indicators of response to targeted therapy and immunotherapy, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study assessed the frequency of MSI status and HER\u20102 expression in a pretreated sample of Iranian patients with gastric and gastroesophageal (GE) adenocarcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>We conducted HER\u20102\/neu expression and mismatch repair (MMR) system analyses on specimens from patients with gastric and GE adenocarcinoma at the Cancer Institute of Iran. Archival tissues from 135 mainly pre\u2010treated surgical specimens of gastric adenocarcinoma cases were used for HER\u20102 analysis, and 66 specimens were used for MSI analysis. All specimens were tested for HER\u20102 amplification, revealing that 11 patients (8.1%) had HER\u20102 amplification, and three out of 66 examined patients exhibited MSI\u2010H. Patients with HER\u20102 overexpressed specimens had a shorter median overall survival (OS) compared with HER\u20102 negative cases (21\u2009months (95% CI: 1.4\u201340.6) vs. 31\u2009months (95% CI: 22.9\u201339), <jats:italic>p<\/jats:italic>\u2009=\u20090.18). The median disease\u2010free survival (DFS) for HER\u20102 positive and negative patients was 15 and 28\u2009months, respectively (<jats:italic>p<\/jats:italic>\u2009=\u20090.25). The estimated median OS and DFS for patients with negative MSI were 26 and 20\u2009months, respectively. However, none of the patients with MSI\u2010positive status experienced recurrence, metastases, or death within the follow\u2010up period; thus, MSI\u2010H patients had a significantly improved OS and DFS (<jats:italic>p<\/jats:italic>\u2009=\u20090.018 and 0.020).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>\u20102 expression, while less common in our Iranian population compared with North American or Western European countries, showed a nonsignificant trend toward poor outcomes in patients with gastric adenocarcinoma. <jats:styled-content style=\"fixed-case\">MSI<\/jats:styled-content>\u2010H status was highly infrequent in our population, suggesting that immunotherapy may not be a beneficial treatment for a significant fraction of Iranian patients with gastric adenocarcinoma. However, a minority may still benefit from it. <jats:styled-content style=\"fixed-case\">MSI<\/jats:styled-content>\u2010H was associated with reduced perineural invasion and improved <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DFS<\/jats:styled-content>. Therefore, this hypothesis warrants further investigation in clinical trials to underscore the prognostic significance of <jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>\u20102 and <jats:styled-content style=\"fixed-case\">MSI<\/jats:styled-content> status and the value of molecular profiling in guiding personalized treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.70314","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T07:21:07Z","timestamp":1756106467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human Epidermal Growth Factor Receptor 2 [<scp>HER<\/scp>\u20102\/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of Iran"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1507-4494","authenticated-orcid":false,"given":"Samaneh","family":"Salarvand","sequence":"first","affiliation":[{"name":"Department of Clinical and Anatomical Pathology, Cancer Institute, School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-8494","authenticated-orcid":false,"given":"Abbas","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine Ahvaz Joundishapur University of Medical Sciences  Ahvaz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Shahsiah","sequence":"additional","affiliation":[{"name":"Department of Clinical and Anatomical Pathology, Cancer Institute, School of Medicine Tehran University of Medical Sciences  Tehran 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