The HER2 oncoprotein is a membrane-associated receptor with tyrosine kinase activity that is overexpressed in several solid tumors and is associated with poor prognosis. However, its role in renal cancer remains unclear. This study aimed to evaluate HER2 expression in renal cell carcinoma and its relationship with prognostic factors.
A total of 110 renal epithelial tumor samples were analyzed. Immunohistochemistry and immunofluorescence were performed using antibodies against HER2, hypoxia-inducible factor α (HIF1α), and EPAS1. Associations with clinicopathological parameters were evaluated using the Chi-square test.
Renal cell carcinoma occurred predominantly in males and was associated with larger tumor size. HER2 expression was detected specifically in the clear cell renal cell carcinoma (ccRCC) subtype. Membranous HER2 expression was positive (3+) in 32% of cases and equivocal (2+) in 47%. Nuclear HER2 localization was observed in 33% of tumors. Membranous HER2 expression was associated with EPAS1/HIF2 expression, whereas nuclear HER2 expression was associated with higher Fuhrman nuclear grades (III-IV). Membranous HER2 was detected in both early (stage I) and advanced clinical stages (III-IV).
HER2 expression in ccRCC occurs in both membranous and nuclear compartments. Membranous HER2 is associated with EPAS1/HIF2 signaling, whereas nuclear HER2 localization correlates with higher Fuhrman nuclear grades. These findings suggest that HER2 may represent a potential therapeutic target and that its nuclear localization may serve as a marker of poor prognosis.
Cancer diagnosis & prognosis. 2026 Jul 01*** epublish ***
María Alicia Cortés, Héctor Marcelo Marín, Nadia Barbás, Rosalia Cordo-Ruso, Lucia Rott, Gustavo Emilio Giusiano, Luis Antonio Merino
CONICET- Faculty of Medicine, National University of the Northeast, Corrientes, Argentina., Institute of Regional Medicine, National University of the Northeast, Chaco, Argentina., Pathology Service, JR Vidal Hospital, Corrientes, Argentina., Laboratory of Molecular Mechanisms of Carcinogenesis, Institute of Biology and Experimental Medicine (IBYME-CONICET), Buenos Aires, Argentina.