Abstract 2393: Kidneys of VHL patients reveal the origin of renal clear cell carcinoma

VHL disease is a classic tumor suppressor gene syndrome characterized by development of specific types of tumors in selective organs with nervous system and kidney being most consistently affected. Detailed studies on human spinal cord and cerebellum have previously revealed earliest stages of CNS tumorigenesis and the morphologic sequence resulting in development of frank tumors. To elucidate earliest stages of renal clear cell carcinoma, we performed a similar approach in kidney tissues of four VHL patients and three sporadic control cases. From all cases, blocks of interest were procured, followed by serial sectioning and 3dimensional reconstruction of potential precursor lesions. The results reveal an abundance of foci with aberrant mesonephric clear cell proliferations that initially develop along the tubular lining, but have the potential to aggregate within individual tubules. This stage is followed by microscopic invasive clear cell aggregations which represent tumor precursor structures. This study presents evidence for a consistent morphologic sequence for renal clear cell carcinogenesis. Molecular analysis of early steps within this sequence will allow for identification of earliest genetic and proteomic changes in the future. Therapeutic targeting of earliest changes may allow to develop preventive strategies for renal cancer development for VHL patients, potentially also for the non-VHL population. Citation Format: Mayyan Mubarak, Samuel Sommaruga, David Voigt, Xiacao Xu, Steve Kim, Ailin Song, Alexander O. Vortmeyer. Kidneys of VHL patients reveal the origin of renal clear cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2393.