In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 411-411
Abstract:
411 Background: The presence of sarc elements in pts with RCC portends a poor prognosis. Some studies have focused on epithelial-to-mesenchymal transition (EMT) as a driver of sarc ccRCC; however, the potential role of other targetable entities is unknown. Methods: From an institutional database, we identified 13 pts with metastatic sarc ccRCC and 13 pts with metastatic ccRCC lacking sarc elements matched by age and risk group. All patients had available FFPE tissue derived from nephrectomy. For a limited sample of 5 pts with sarc ccRCC, RNA sequencing was performed on microdissected cc, sarc, and benign renal cortical sections from FFPE blocks. Reads were aligned to hg19 genome with Tophat v2.0. IHC was used to explore expression of implicated genes in the entire matched cohort of 26 pts. Results: With respect to RNA sequencing analysis for 5 pts with sarc ccRCC, reads had between 4% and 24% exon coverage. Hierarchical clustering demonstrated that most samples were clustered by patient, not by disease state (i.e., sarc vs non-sarc), suggesting that inter-patient variation is large. However, comparisons between cc and sarc components for these 5 pts demonstrated a significant increase in cell growth pathways, with the most highly enriched gene ontology pathways being M-phase, cell cycle, mitosis and aurora kinase pathways. No EMT-related pathways were found to be enriched. IHC assessments of VEGF and mTOR pathways were performed, given their purported role in RCC cell growth. While no differences were noted in pVEGFR2, higher pS6K staining was noted in both the sarc and non-sarc components of pts with sarc ccRCC relative to pS6K staining in tumor tissue derived from ccRCC pts lacking sarc elements (p 〈 0.05 for both). No differences in EMT marker expression were noted (specifically, E-cad, N-cad and Twist); IHC assessments for aurora kinases A and B will be reported. Conclusions: Although cytotoxic agents and VEGF-directed therapies have been explored in sarc ccRCC, the finding of mTOR pathway activity underscores the need to examine mTOR inhibitors in this disease. Furthermore, emerging agents targeting aurora kinases may have a role in sarc ccRCC.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2014.32.4_suppl.411
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2014
detail.hit.zdb_id:
2005181-5
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