Proteomic Distinction of Renal Oncocytomas and Eosinophilic Chromophobe Renal Cell Carcinomas

ABSTRACT: Background Renal oncocytomas (ROs) are benign epithelial tumors of the kidney that may progress into malignant chromophobe renal cell carcinoma (chRCCs), with the latter constituting 5 – 7 % of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and chRCCs in order to better understand distinguishing protein patterns. Methods We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases lacking any overlap with the smaller proteomic cohort. Results: At 1 % false discovery rate, we identified > 3900 proteins, of which >2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO. Conclusion We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

SUBMITTER: Oliver Schilling  

LAB HEAD: Oliver Schilling

PROVIDER: PXD009300 | Pride | 2018-08-13

REPOSITORIES: Pride