519 Background: Presence of sarcomatoid features in Renal Cell Carcinoma (sRCC) tumors signals aggressive clinical behavior and poor prognosis compared to Clear Cell Renal Cell Carcinoma (ccRCC). However, the underlying gene expression patterns of sRCC are poorly understood. We sought to categorize ccRCC and sRCC gene expression subtypes and compare survival outcomes, as well as evaluate whether sRCC gene expression patterns are similar to non-renal sarcomas. Methods: We identified 511 ccRCC cases, of which 36 had a sarcomatoid component from The Cancer Genome Atlas. Enrichment analysis was used to measure associations between gene expression signatures for soft tissue sarcomas and expression profiles of sRCC and ccRCC cases measured by RNA-Seq. The resulting scores were used to identify distinct patient groups using K-means clustering. Overall survival (OS) was evaluated by Kaplan-Meier, log rank, and Cox regression methods. Results: Our analysis identified 4 distinct clusters that differ in enrichment for soft-tissue sarcoma gene expression profiles. The clusters showed significantly different OS distributions (p-value<0.001 log rank). Most sRCC cases (69%) segregated into a single cluster with the worst prognosis. Among ccRCC cases, 57% of patients with higher levels of sarcoma signature enrichment were associated with a shorter OS, which is independent of tumor stage. 5-year/median OS survival estimates for ccRCC cases in the 4 clusters, by increasing levels of sarcoma profile enrichment, were 83%/NR, 75%/NR, 67%/90.9 mo, and 49%/56.7 mo. We also validated existence of these clusters in another sRCC cohort (Sircar 2015). Conclusions: We identified strong associations between sarcoma expression signatures and gene expression profiles of sRCC. We also found that 57% of morphologically non-sRCC cases demonstrate enrichment for sarcoma expression signatures, and these patients have worse OS than their non-sarcoma enriched ccRCC counterparts. The presence of sarcoma expression signatures has not been previously evaluated in RCC. These signatures portend poor survival and may be clinically actionable, as they describe unique subtypes of RCC that may not correspond to histologic characterization.
MP78-14 RELATIONSHIP BETWEEN THE GENE EXPRESSION PROFILES OF RENAL CELL CARCINOMA AND BOTH PROGNOSTIC MOLECULAR CLASSIFICATION AND RESPONSE TO TARGETED THERAPY
