Renal oncocytoma (RO) accounts for 5% of renal cancers and generally behaves as a benign tumor with favorable long-term prognosis. It is difficult to confidently distinguish between benign RO and other renal malignancies, particularly chromophobe renal cell carcinoma (chRCC). Therefore, RO is often managed aggressively with surgery. We sought to identify molecular biomarkers to distinguish RO from chRCC and other malignant renal cancer mimics. In a 44-patient discovery cohort, we identified a significant differential abundance of nine genes in RO relative to chRCC. These genes were used to train a classifier to distinguish RO from chRCC in an independent 57-patient cohort. The trained classifier was then validated in five independent cohorts comprising 89 total patients. This nine-gene classifier trained on the basis of differential gene expression showed 93% sensitivity and 98% specificity for distinguishing RO from chRCC across the pooled validation cohorts, with a c-statistic of 0.978. This tool may be a useful adjunct to other diagnostic modalities to decrease the diagnostic and management uncertainty associated with small renal masses and to enable clinicians to recommend more confidently less aggressive management for some tumors. PATIENT SUMMARY: Renal oncocytoma is generally a benign form of kidney cancer that does not necessarily require surgical removal. However, it is difficult to distinguish renal oncocytoma from other more aggressive forms of kidney cancer, so it is treated most commonly with surgery. We built a classification tool based on the RNA levels of nine genes that may help avoid these surgeries by reliably distinguishing renal oncocytoma from other forms of kidney cancer.
European urology. 2020 Sep 21 [Epub ahead of print]
Patrick D McGillivray, Daiki Ueno, Aydin Pooli, Neil Mendhiratta, Jamil S Syed, Kevin A Nguyen, Peter G Schulam, Peter A Humphrey, Adebowale J Adeniran, Paul C Boutros, Brian Shuch
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Department of Urology, Yale School of Medicine, New Haven, CT, USA., Department of Pathology, Yale School of Medicine, New Haven, CT, USA., Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Institute for Precision Health, University of California Los Angeles, Los Angeles, CA, USA., Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: .