• Rola M Saleeb, Fadi Brimo, Mina Farag, Alexis Rompré-Brodeur, Fabio Rotondo, Vidya Beharry, Samantha Wala, Pamela Plant, Michelle R Downes, Kenneth Pace, Andrew Evans, Georg Bjarnason, BartlettJohn M SJMS, and George M Yousef.
• *Department of Laboratory Medicine, and the Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital †Department of Laboratory Medicine and Pathobiology, University of Toronto ∥Department of Pathology **Division of Medical Oncology and Hematology, Sunnybrook Health Sciences Centre ¶Department of Surgery, Division of Urology, St. Michael's Hospital #Department of Pathology, University Health Network ††Ontario Institute for Cancer Research, Toronto, ON Departments of ‡Pathology §Urology, McGill University Health Center, Montreal, QC, Canada.
• Am. J. Surg. Pathol. 2017 Dec 1; 41 (12): 1618-1629.

AbstractPapillary renal cell carcinoma (PRCC) has 2 histologic subtypes. Almost half of the cases fail to meet all morphologic criteria for either type, hence are characterized as PRCC not otherwise specified (NOS). There are yet no markers to resolve the PRCC NOS category. Accurate classification can better guide the management of these patients. In our previous PRCC study we identified markers that can distinguish between the subtypes. A PRCC patient cohort of 108 cases was selected for the current study. A panel of potentially distinguishing markers was chosen from our previous genomic analysis, and assessed by immunohistochemistry. The panel exhibited distinct staining patterns between the 2 classic PRCC subtypes; and successfully reclassified the NOS (45%) cases. Moreover, these immunomarkers revealed a third subtype, PRCC3 (35% of the cohort). Molecular testing using miRNA expression and copy number variation analysis confirmed the presence of 3 distinct molecular signatures corresponding to the 3 subtypes. Disease-free survival was significantly enhanced in PRCC1 versus 2 and 3 (P=0.047) on univariate analysis. The subtypes stratification was also significant on multivariate analysis (P=0.025; hazard ratio, 6; 95% confidence interval, 1.25-32.2). We propose a new classification system of PRCC integrating morphologic, immunophenotypical, and molecular analysis. The newly described PRCC3 has overlapping morphology between PRCC1 and PRCC2, hence would be subtyped as NOS in the current classification. Molecularly PRCC3 has a distinct signature and clinically it behaves similar to PRCC2. The new classification stratifies PRCC patients into clinically relevant subgroups and has significant implications on the management of PRCC.

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