Abstract
Abstract High-grade gliomas are some of the most lethal forms of human cancers. In glioblastomas, which are the most frequent and malignant type of glioma, microRNA-21 (miR21) has recently been suggested to be strongly upregulated. Until now, miR21 expression analysis has mainly been carried out using PCR methods, hence little is known about the cellular localization of miR21 in gliomas. Studies of other cancers have demonstrated miR21's prognostic value as well as roles in invasion, growth and anti-apoptosis. This suggests that miR21 is a potential therapeutic target as well as a promising novel prognostic marker in gliomas. The aim of the present study was therefore to investigate the expression of miR21 in gliomas and correlate it with tumor grade and overall survival using the new possibilities of locked nucleic acid (LNA) based in situ hybridization. We used 193 formalin-fixed paraffin embedded astrocytic and oligodendroglial brain tumors of increasing grade (WHO I-IV). Sections from these tumors were stained by a robust in situ hybridization assay using high-affinity LNA probes that specifically detect miR21. The expression of miR21 was revealed as a blue chromogenic staining reaction. Using advanced image analysis, the area of the staining reaction was measured by a trained pixel classifier on images recorded by stereological principles. The optimal sampling fraction was estimated to be 10%. The results showed that the miR21 signal was localized to blood vessels and populations of dispersed single cells. Moreover, the characteristic gemistocytic tumor cells seemed to display a distinct staining reaction. The miR21 signal increased with tumor grade and a very high individual signal variation was observed, especially among glioblastomas. When comparing the miR21 signal with overall survival, a high signal was associated with shorter survival, but in multivariate analysis this was not independent of grade. In conclusion miR21 is localized in both tumor cells and blood vessels in gliomas. A high miR21 expression appears to be associated with tumor grade and shorter survival underlining the importance of miR21 in glioma biology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1156. doi:10.1158/1538-7445.AM2011-1156
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