HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches.

Autor: Freitas MB; Department of Medical Oncology of Unidade Local de Saúde (ULS) de São João, 4200-319 Porto, Portugal., Gullo I; Department of Pathology of Unidade Local de Saúde (ULS) de São João, 4200-319 Porto, Portugal.; Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-329 Porto, Portugal.; Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal., Leitão D; Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-329 Porto, Portugal., Águas L; Department of Medical Oncology of Unidade Local de Saúde (ULS) de São João, 4200-319 Porto, Portugal.; Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal., Oliveira C; Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal.; Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal.; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal., Polónia A; Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal.; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal.; Instituto de Investigação, Inovação e Desenvolvimento, Fundação Fernando Pessoa (FP-I3ID), 4249-004 Porto, Portugal., Gomes J; Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal.; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal., Carneiro F; Department of Pathology of Unidade Local de Saúde (ULS) de São João, 4200-319 Porto, Portugal.; Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-329 Porto, Portugal.; Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal.; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal., Reis CA; Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal.; Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal.; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal.; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal., Duarte HO; Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal.; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 Mar 20; Vol. 16 (6). Date of Electronic Publication: 2024 Mar 20.
DOI: 10.3390/cancers16061227
Abstrakt: Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
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