HER2 Expression and Nuclear Localization in Clear Cell Renal Cell Carcinoma: Implications for Prognosis and Therapeutic Targeting

Rákkutatás · Renal cell carcinoma · ERBB2

HER2 is expressed in both membranous and nuclear compartments of clear cell renal cell carcinoma (ccRCC); membranous HER2 is associated with EPAS1/HIF2 signaling, while nuclear HER2 correlates with higher Fuhrman nuclear grades, indicating HER2 as a potential therapeutic target and a marker of poor prognosis.

The HER2 oncoprotein is a membrane-associated receptor tyrosine kinase that is overexpressed in several solid tumors and is associated with poor prognosis. Its role in renal cancer is unclear. This study evaluated HER2 expression in 110 renal epithelial tumor samples using immunohistochemistry and immunofluorescence. HER2 was specifically detected in the clear cell renal cell carcinoma (ccRCC) subtype. Membranous HER2 was 3+ in 32 % of cases and 2+ in 47 %. Nuclear HER2 was observed in 33 % of tumors. Membranous HER2 expression correlated with EPAS1/HIF2 signaling, whereas nuclear HER2 expression correlated with higher Fuhrman nuclear grades (III–IV). Membranous HER2 was present in both early (stage I) and advanced (III–IV) stages. These findings suggest that HER2 may represent a potential therapeutic target and that its nuclear localization may serve as a marker of poor prognosis.

HER2 is a well‑established therapeutic target in several cancers, yet its prognostic and therapeutic relevance in clear cell renal cell carcinoma remains undefined. Defining HER2 expression patterns in ccRCC could identify patients who may benefit from HER2‑directed therapies and provide a novel biomarker to improve risk stratification.

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