Gastroesophageal carcinomas, including gastroesophageal adenocarcinoma (GEA) and esophageal squamous cell carcinoma (ESCC), pose a global health challenge due to their heterogeneity. The approach to diagnosis and treatment should first differentiate between GEA and ESCC. Over the past decade, therapies for metastatic or advanced GEA/ESCC have expanded, with several new therapeutic targets alongside trastuzumab for metastatic HER2-positive GEA. Four key biomarkers are essential for targeted therapy: HER2 overexpression/amplification, deficient mismatch repair/microsatellite instability (dMMR/MSI), PD-L1, and Claudin18.2 expression. Immunohistochemistry is the recommended method for these biomarkers evaluation. In addition, the assessment of biomarkers like FGFR2b is likely to become routine in the near future. Experts from the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) have formed a consensus to optimize biomarker detection and usage in clinical practice. Their recommendations aim to improve personalized treatment strategies for GEA and ESCC patients, integrating new diagnostic insights into routine care.
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