HER2 in Clear Cell Renal Cell Carcinoma: Expression and Novel Targeting

Purpose: The HER2 oncoprotein, a membrane-associated protein with tyrosine kinase activity, is overexpressed in many solid tumours. Its overexpression is associated with poor prognosis and disease progression. In kidney cancer, there is no molecular marker to guide patient treatment and prognosis. Materials and Methods: For the study, 110 biopsy samples obtained from patients with renal epithelial tumors were used. Immunohistolabeling using HER2, HIF1α and EPAS1 specific antibody. Correlation with clinical aspects and prognostic factors by chi square test. Results: In our population, renal cells carcinoma (RCC) is predominantly distributed in men and it is larger in size, increasing in the 30-40 age range, with a peak frequency between 51-60 and 61-79 years. HER2 expression only in the histological phenotype of clear cell renal cell carcinoma (ccRCC). It was detected positive (3+) in 32% of cases and equivocal (2+) in 47%. HER2 expression in the nucleus in 33% of cases was also observed. Membranous HER2 expression was correlated with HIF2, but not with HIF1. Membranous HER2 expression was observed in Fuhrman grade II tumors, while nuclear HER2 expression was associated with grades III and IV. Finally, it was found that membranous HER2 expression with low (I) and high (III and IV) clinical stages was observed. Conclusions: RCC is more frequent in males, with HER2 expression in membrane and nucleus in ccRCC. Membranous HER2 is linked to EPAS1/HIF2 and stages (I/III); nuclear HER2 to Fuhrman grades (III/IV).