Abstract 2464: Papillary renal cell carcinoma, proposal of a new classification system based on integrated molecular, histological and clinical analysis

Abstract

Abstract Background: Papillary Renal Cell Carcinoma (PRCC) is divided into histological subtypes 1 and 2. Type 2 is known to have worse clinical behavior. A number of PRCC cases (~ 50%), fail to meet all reported morphological criteria for either type, hence are best characterized as PRCC not otherwise specified (NOS). There are yet no reliable markers to resolve the PRCC NOS category. That in turn reflects the clinical dilemma of how to manage these patients. Experimental Design: PRCC patient cohort of 115 cases was selected for the study. Cases were subtyped histologically into PRCC types 1, 2 and NOS. Potentially distinguishing markers ABCC2, CA9, SAll4, and BCL2 selected from our previous genomic analysis, were assessed by immunohistochemistry (IHC). A total of 24 cases were further selected for molecular analysis using miRNA expression and copy number variation (CNV). Univariate and multivariate survival analysis were performed using Log rank test and cox proportionate hazards. Results: Markers ABCC2, CA9 exhibited distinct staining patterns between the two classic PRCC subtypes; and successfully classified many of the PRCC NOS (45%) cases. Moreover, immunomarkers revealed a third distinct subtype of PRCC (35% of the PRCC cohort). Molecular testing using miRNA expression and CNV analysis confirmed the presence of three distinct molecular signatures corresponding to the 3 subtypes. On univariate analysis DFS was significantly enhanced in the type1 versus 2& 3 (p value 0.047). PRCC subtyping retained significance on multivariate analysis (p value 0.025, HR:6, 95% CI 1.25 to 32.2) . Conclusion: We propose a new classification system of PRCC integrating morphological, immunophenotypical, and molecular analysis. Our classification reveals a 3rd PRCC subtype that was not previously described. This subtype has overlapping morphology of with PRCC types 1 and 2, hence would be subtyped as PRCC NOS in the current classification. Molecularly PRCC type 3 has a distinct signature and clinically it behaves similar to PRCC type 2. The new classification stratifies PRCC patients into clinically relevant subgroups and has significant future implications on the management of PRCC. Citation Format: Rola Saleeb, Mina Farag, Fadi Brimo, Fabio Rotondo, Pamela Plant, George Yousef. Papillary renal cell carcinoma, proposal of a new classification system based on integrated molecular, histological and clinical analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2464. doi:10.1158/1538-7445.AM2017-2464