Description:
<jats:title>Abstract</jats:title>
<jats:p>The identification of reliable indicators of prognosis, which may allow the stratification of patients according to different risk at diagnosis isan important aspect of translational research in Ewing sarcoma (ES). In this paper, we validated our previous evidence showing how expression of miR34a in ES tumor samples at diagnosis was signficantly associated with tumor progression (Nakatani F. J Pathol 2012). Here we analyzed a different series of speciments derived from very controlled and homogeneously treated non-metastatic ES patients, and we compared evaluation of miR34a by RT-PCR using frozen samples with that obtained by in situ hybridization on paraffin-embedded samples . The median follow-up of the 109 EWS patients was 90 months (range 9 to 241 months). 68 patients (63%) remained continuously free of disease and 41 (38%) relapsed. Expression of miR34a was evaluated by qRT-PCR using TaqMan miRNA assay kit and/or by in situ hybridization ISH optimization kit from Exiqon. High expression of miR34a was significantly related to better EFS and OVS : 5-year EFS was 74% for the 55 patients with high expression of miR34a and was 51% for the 54 patients with low expression (p = 0.004); 5-year OVS was 83% in high-expressors and 58% in low-expressors . By multivariate Cox regression analysis, the value of low miR-34a expression as well as of non-total necrosis and high LDH were all confirmed as independent risk factors associated with poor outcome. miR34a was also evaluated by ISH on TMA. miRNA expression by ISH correlates with that obtained by RT-PCR (r=0.59, p&lt;0.0001, Spearman test). Although not significant, high expression of miR34a evalutated on tissue microarray still shows an association with better outcome (p=0.19). Expression of miR34a inversely correlated with expression of cyclin D1 mRNA, as well as with Ki-67 labelling. In contrast positive association was observed with YY1, a transcription factor that regulates a dazzling list of genes and whose role in malignancy is complex and has just started to emerge. The value of miR34a as predictor was higher than that of these specific targets, indicating a more complex relationship with tumor malignancy.</jats:p>
<jats:p>Citation Format: Katia Scotlandi, Maria Teresa Marino, Andrea Grilli, Piero Picci, Alessandra Carè, Claudio Tripodo, Stefano Ferrari. miR34a: A valuable indicator of differential outcome of Ewing sarcoma patients with complex functions. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A42.</jats:p>