Proteomic distinction of renal oncocytomas and chromophobe renal cell carcinomas |
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Authors: | Vanessa Drendel Bianca Heckelmann Christoph Schell Lucas Kook Martin L Biniossek Martin Werner Cordula A Jilg Oliver Schilling |
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Institution: | 1.Institute for Surgical Pathology, Medical Center – University of Freiburg, Faculty of Medicine,University of Freiburg,Freiburg,Germany;2.Institute of Molecular Medicine and Cell Research, Faculty of Medicine,University of Freiburg,Freiburg,Germany;3.German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ),Heidelberg,Germany;4.Department of Urology, Medical Center – University of Freiburg, Faculty of Medicine,University of Freiburg,Freiburg,Germany;5.Comprehensive Cancer Center Freiburg,Medical Center – University of Freiburg,Freiburg,Germany;6.BIOSS Centre for Biological Signaling Studies,University of Freiburg,Freiburg,Germany |
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Abstract: | BackgroundRenal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 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 early-stage chRCCs in order to better understand distinguishing protein patterns.MethodsWe 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.ResultsAt 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.ConclusionWe 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. |
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