European urology supplements vol:10 issue:2 pages:235-236
EAU Annual Congress edition:26 location:Vienna, Austria date:18-22 March 2011
Introduction & Objectives: Sunitinib is the first line targeted therapy for stage IV clear cell renal cell carcinoma (ccRCC) in good and intermediate risk patients
according to Memorial Sloan-Kettering Cancer Center criteria. Objective response is reached in ±40% of patients. MicroRNA’s from the miR-200 family are linked with
tumour aggressiveness, progression and therapy resistance. Down-regulation of microRNA-141, a member of the miR-200 family, is linked with proliferation and invasion through epithelial-to-mesenchymal transition in various types of cancer and causes gain of function of oncogenes in ccRCC. We aim to identify whether these epigenetic mechanisms might be linked with sunitinib response.
Materials & Methods: Fresh-frozen ccRCC tissue samples from a single institution nephrectomy-specimens database of patients who underwent sunitinib treatment between 2006 and 2010 as first-line targeted therapy were included in the study population. Bad responders were considered those patients with progressive disease within 6 months. Patients with progression free survival of more than 1 year were considered good responders. Currently 20 fresh-frozen nephrectomy ccRCC specimens have been analyzed. Fold expression of micro-RNAs was attained by means of real-time qPCR and statistical analysis was performed using
a Mann-Whitney U test. Validation by means of in situ hybridization with a specific probe for microRNA-141 was performed on formalin-fixed paraffin embedded ccRCC tissue of the same patients.
Results: Expression of microRNA-141 was significantly lower in the bad responders group (p=0,0098) (figure 1A). In situ hybridization of microRNA-141 shows that bad responders (figure B1) display lower expression of microRNA-141 as compared to good responders (figure B2). Moreover, it was noted that in samples of good responders expression was predominantly seen in the periphery of the tumour.
Conclusions: Down-regulation of microRNA-141 could play an important role in sunitinib-resistant ccRCC suggesting epithelial-to-mesenchymal transition as an important underlying mechanism. A larger patient population as well as functional data will be obtained to validate these results.