Data from The Transcription Factor Evi-1 Is Overexpressed, Promotes Proliferation, and Is Prognostically Unfavorable in Infratentorial Ependymomas

<div>Abstract<p><b>Purpose:</b> Ependymomas are glial tumors of presumably radial glial origin that share morphologic similarities with ependymal cells. The molecular genetics of ependymomas of supratentorial, infratentorial, and spinal location is heterogeneous. We aimed at identifying pathways operative in the development of infratentorial ependymomas.</p><p><b>Experimental Design:</b> To do so, gene expression profiles of tumor cells laser microdissected from infratentorial ependymomas (<i>n</i> = 15) were compared with that of nonneoplastic ependymal cells laser microdissected from autopsy tissue (<i>n</i> = 7).</p><p><b>Results:</b> Among 31 genes significantly overexpressed (>5-fold) in ependymomas, transcription factor <i>EVI1</i> (ecotropic viral integration site 1) showed the highest overexpression (35-fold). Evi-1 protein expression could be confirmed in formalin-fixed, paraffin-embedded samples of 26 of 28 infratentorial ependymomas but only in 7 of 47 nonependymal glial tumors (<i>P</i> < 0.001). Furthermore, <i>MDS1/EVI1</i> fusion transcripts were detectable in 17 of 28 infratentorial ependymomas and significantly correlated with MGMT (O6-methylguanine-DNA-methyltransferase) promoter hypermethylation (<i>P</i> < 0.05). In primary infratentorial ependymoma cells, transfection with <i>EVI1</i>-specific siRNAs resulted in significant growth inhibition [48 hours: 87% ± 2% and 74% ± 10% as compared with control (mean ± SD; <i>P</i> < 0.001)]. The prognostic role of <i>EVI1</i> could further be validated in an independent cohort of 39 infratentorial and 26 supratentorial ependymomas on the basis of mRNA expression profiling. Although in supratentorial ependymomas <i>EVI1</i> expression status had no prognostic impact, in infratentorial ependymomas, high <i>EVI1</i> expression was associated with shorter overall survival and progression-free survival.</p><p><b>Conclusions:</b> To conclude, the transcription factor Evi-1 is overexpressed in infratentorial ependymomas, promotes proliferation of ependymal tumor cells, and is prognostically unfavorable. <i>Clin Cancer Res; 17(11); 3631–7. ©2011 AACR</i>.</p></div>