Sarcomatoid Renal Cell Carcinoma Shows a Distinct Transcriptomic Profile That Is Not Associated with Epithelial to Mesenchymal Transition Markers
Kanishka Sircar, Ted Majewski, Khalida Wani, Jon McDonald, Keith Baggerly, Pheroze Tamboli, Bogdan Czerniak, Kenneth Aldape. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Renal cell carcinoma (RCC) accounts for 13000 cancer deaths yearly in the USA with prognosis most strongly correlated to pathologic tumor stage. Sarcomatoid transformation, a histologic change that occurs in approximately 5% of RCC, is long known to predict for an aggressive clinical course with limited therapeutic options and a median overall survival of under 17 months even in localized disease. Further advancement that requires a molecular understanding of sarcomatoid change in RCC has been hindered, in part, by the difficulty in obtaining suitable sarcomatoid RCC tissues. We sought to characterize the transcriptome of sarcomatoid RCC, particularly with respect to epithelial to mesenchymal transition (EMT) markers and in comparison with clinically advanced non-sarcomatoid RCC.
Design: Archived clinical samples from 23 patients with sarcomatoid RCC were selected that had at least 15% sarcomatoid (S) and epithelioid (E) components. The epithelioid component was restricted to clear cell RCC histology. As controls, we used the epithelial component (E*) from 54 patients with non-sarcomatoid clear cell RCC (stage 4, n=40; stages 1-3, n=14). Lesional foci (E*, E, S) were macrodissected from formalin fixed paraffin embedded tissues and RNA was extracted using the DASL protocol. The transcriptomic profile of all lesions (n=100: 23 E, 23 S, 54 E*) was assessed by whole genome gene expression microarray (Illumina Array HumanRef-8 v3).
Results: Unsupervised clustering analysis showed no significant differences in global gene expression between the epithelioid (E) and sarcomatoid (S) groups in sarcomatoid RCC. Supervised analysis for 68 EMT probes likewise showed no association between E and S groups or the E* and E/S groups. Most non-sarcomatoid RCC (E*, n=45/54) showed separation from sarcomatoid RCC with two expression patterns seen: high in E*, low in E/S; high in E/S only. A subset of non-sarcomatoid RCC (E*, n=9/54) that were all stage 4 (n=9/40) did, however, show overlap with sarcomatoid RCC: high in both E* and E/S.
Conclusions: This first ever genome wide transcriptional profiling study of sarcomatoid RCC showed that the histologically separable epithelioid and sarcomatoid components could not be distinguished by gene expression pattern, including for EMT genes. Our data suggests two signatures for tumor aggressiveness in clear cell RCC with a subset of advanced non-sarcomatoid RCC showing a molecular transition to a sarcomatoid phenotype.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 167, Tuesday Morning