Abstract
478 Background: Sarcomatoid differentiation is an uncommon histological finding in renal cell carcinoma (RCC) that may develop from any RCC subtype and is associated with a very poor prognosis. The identification of genetic alterations that drive this aggressive phenotype could aid in the development of more effective targeted therapies. In this study, we aimed to identify unique copy number alterations (CNAs) in patients with sarcomatoid RCC when compared to those with other RCC subtypes. Methods: Genomic copy number analysis was performed using single nucleotide polymorphism (SNP)-based microarrays on tissue extracted from the tumors of 80 patients (9 with sarcomatoid features (sRCC), 39 clear cell (ccRCC), 26 papillary (pRCC) and 6 chromophobe RCC (chRCC)) who underwent renal mass excision between 2010 - 2014. Statistical analysis was performed using Kaplan Meier (KM) survival analysis, t-tests and Fisher exact tests where appropriate. Results: sRCC tumors exhibited significantly higher numbers of CNAs when compared to ccRCC, pRCC and chRCC (mean 20.1 vs. 6.6 vs. 7.0 vs. 6.3, respectively; p <0.0001). The most common copy number losses occurred in chromosome arms 1p, 3p, 9q, 15q, 18q, 21q, and 22q, with losses of 9q (88%), 15q (77%), 18q (66%), and 22 (77%) being unique among sRCC tumors when compared to the other 3 histologies. The most common copy number gains were in chromosome arms 1q, 8q, 17q, and 20p/q, with 1q (55%) and 8q (66%) gains unique when compared to the other 3 histologies. Of the sRCC tumors, 3 arose from ccRCC, 2 from pRCC and 4 from unclassified RCC. sRCC was associated with worse survival compared to ccRCC, pRCC and chRCC on KM analysis (p=0.0006), and higher rates of lymph node positivity (77% vs. 3% vs. 12% vs. 0%, respectively; p<0.0001) and metastases (100% vs. 13% vs. 4% vs. 0%, respectively; p<0.0001) on presentation were observed with sRCC. Conclusions: Sarcomatoid differentiation in RCC is associated with a high rate of chromosomal changes with unique copy number alterations including losses of 9q, 15q, 18q and 22q and gains of 1q and 8q. Identification and validation of candidate driver genes or tumor suppressor loci within these chromosomal regions may help identify targets for future therapies.
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