Sarcomatoid and Rhabdoid RCC Show a Similar, Poor Prognosis Molecular Signature That Is Separable from Non-Sarcomatoid RCC
Kanishka Sircar, Ted Majewski, Suk-Young Yoo, Lalit Patel, Khalida Wani, Pheroze Tamboli, Bogdan Czerniak, Keith Baggerly, Ken Aldape. MD Anderson Cancer Center, Houston, TX
Background: Sarcomatoid and rhabdoid transformation are predictors of adverse prognosis in renal cell carcinoma (RCC) with the majority of patients presenting with metastatic disease. Molecular characterization of these aggressive variants has been hampered by inadequate pathologically annotated frozen tissues. We sought to study sarcomatoid and rhabdoid RCC compared with clinically advanced non-sarcomatoid RCC using gene expression profiling and next generation sequencing approaches.
Design: Samples from 27 patients with sarcomatoid clear cell RCC (stage 4, n=20; stage 3, n=6; stage 2, n=1) and 4 patients with rhabdoid clear cell RCC (stage 4, n=3; stage 3, n=1) were selected. These tumors had a minimum 5 x 5 mm area of pure sarcomatoid (S), rhabdoid (R) and epithelioid (E) histology. As controls, we used the epithelial component (E*) from 41 patients with non-sarcomatoid clear cell RCC (stage 4, n=24; stage 3, n=17). Lesional foci (E*, E, S, R) were macrodissected from FFPE blocks and RNA was extracted using the DASL protocol. The transcriptome was assessed by whole genome expression microarray (Illumina HumanRef-8 v3/v4). Next generation RNA-Seq (Illumina HiSeq) was performed on 3 E/S pairs and 1 E/R pair.
Results: Bioinformatics analysis showed no significant gene expression differences between sarcomatoid (S) and rhabdoid (R) RCC. Non-sarcomatoid RCC (E*) did, however, show many differentially expressed genes (n=683 at FDR of 0.001, P=5.2 10-5) compared to sarcomatoid RCC (E/S). Supervised analysis for good (ccA) and poor (ccB) prognosis probes in RCC showed sarcomatoid RCC to be associated with ccB and non-sarcomatoid RCC to be associated with ccA (P=0.002). RNA-Seq did not show any chromosomal rearrangements in E, S or R samples and it confirmed the similarity in gene expression between E/S and E/R.
Conclusions: Sarcomatoid and rhabdoid RCC are not distinguishable at the gene expression level and may potentially be approached similarly from a clinical standpoint. The molecular signature of sarcomatoid RCC represents the extreme end of poor prognosis RCC and is separable from stage matched non-sarcomatoid RCC. Factors governing the transition from epithelioid to sarcomatoid/rhabdoid morphology remain elusive with no chromosomal translocations detected. The contrast between non-sarcomatoid RCC (E*) and the epithelioid/sarcomatoid (E/S) components of sarcomatoid RCC suggests the potential for developing a panel of biomarkers that can detect sarcomatoid change in RCC.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 169, Monday Afternoon