Single-institutional analysis of patients with clear-cell papillary renal cell carcinoma.

Abstract

512 Background: Recently clear cell papillary renal cell carcinoma (cpRCC) has been recognized as new histologic subtype with immunohistochemical profiles that differentiate it from clear cell (ccRCC) and papillary (pRCC) RCC. Several previous studies highlighted the indolent behaviour of this entity in the reported cases. Our primary objective is to further elucidate the genomic and clinical characteristics of cpRCC. Methods: 44 patients with cpRCC were selected from the MSKCC database with surgery performed between 2007 and 2014. Only tumors with appropriate histological configuration and immunohistochemically confirmed CAIX and CK7 positivity and CD10 negativity were included. Whole exome sequencing (WES) was performed on 5 cpRCC tumor samples and one sample was analyzed by next-generation sequencing (MSK-IMPACT). A further comparison was made to 825 ccRCC and 219 pRCC tumors with initial pT1 diagnosis from our institutional database. Differences in the variables across groups were analyzed with the Chi-Square and the Kruskal–Wallis tests. To visualize and test the survival distribution differences, we used Kaplan–Meier plots and Log-rank tests. Results: Sequencing did not reveal VHL mutations or other known driver mutations commonly seen in ccRCC or pRCC and no recurrent mutations were identified. The median follow up period for cpRCC was 27 months, for ccRCC 59 months and for pRCC 63 months. cpRCC frequently co-occured with ccRCC or other RCC subtypes (17/44 cases). Female patients developed cpRCC significantly more frequently than ccRCC or pRCC (47.7% P<0.001) and Kruskal-Wallis test revealed differences in tumor size between the 3 groups (cpRCC median size 2.5 cm, P<0.001). Recurrence, metastatic development and death from kidney cancer was observed in ccRCC (3.7%, 2.3% and 0.8%) and in pRCC (4.5%, 1.8% and 2%), but not in the cpRCC cohort. Conclusions: cpRCC is genomically distinct from ccRCC and pRCC and lacks driver mutations commonly associated with aggressive disease. The tumors tend to present smaller than other RCC subtypes, commonly co-occur with other RCCs and disproportionately affect women. Extended follow-up of larger cohorts is necessary to confirm the true indolent nature of cpRCC.