Abstract Polycystin-1 (PC1) is a cellular transmembrane protein encoded by the polycystic kidney disease gene (PKD1) prevalently expressed in developing/mature kidney and in autosomal polycystic kidney disease (ADPKD). Limited data are available concerning the PC1 involvement in renal tumorigenesis. Polycystin-1 expression was evaluated by immunohistochemistry (IHC) in 8 clear cell renal cell carcinomas (RCCs), 7 tubulopapilary cell type tumors, 3 solid RCCs developed in patients with von Hippel-Lindau disease (VHL), one RCC developed in a patient on chronic haemodyalisis and one angyomyolipoma in a patient with Tuberous sclerosis (TS). In parallel, the BIZ cell line derived from a high grade clear cell RCC and the WUR cell line derived from a tubulopapillary type RCC, were used to measure the level of PC1 expression by both immunolabeling and immunoblotting analyses. Five cases of clear cell type RCCs, and two tubulopapillary cell type RCCs consistently expressed PC1 with a percentage of labeled neoplastic cells ranging between 15% and 65%. Un the VHL disease-associated renal cell carcinoma, both the tumor cells and cystic tissues areas weakly expressed the PC1 protein. In TS-associated angiomyolipoma, the vascular component was PC1 positive, while the tumor cells were scarcely stained. High level of expression of PC1 was confirmed by both IHC and immunoblotting in WUR RCC cells (80% of labeled cells), while BIZ RCC cells exhibited a moderate PC1 staining (30% of labeled cells). Comparatively, in the normal kidney, consistent level of polycystin 1 was detected in distal tubules, collecting duct, glomerular podocytes and vascular smooth muscle cells. The strongest immunoreactivity against PC1 was observed in epithelial cells lining the cystic components in all ADPKD tissues. In conclusion, the presented data indicate consistent level of expression of the polycystin-1 protein in a number renal cell carcinomas and suggest that PC1 expression is linked to the tumor cell type, being more frequent event in clear cell type RCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2968.