Abstract LB-360: Fluorescence-based co-registration with protein markers reveals distinct cellular compartments for altered microRNA expression in solid tumors

Abstract

Abstract MicroRNAs (miRNAs) are a class of short non-coding regulatory RNA genes, which have been implicated in the control of developmental, physiological and pathological processes. High-throughput profiling experiments have linked altered expression of miRNAs to different types of cancer. To clarify the clinical significance of these expression changes, we developed a sensitive fluorescence-based in situ hybridization (ISH) method to visualize miRNA accumulation within individual cells in formalin-fixed paraffin-embedded tissues. This ISH method was implemented to be compatible with routine automated clinical immunohistochemical (IHC) assays to enable co-detection with protein markers on the same tissue section for co-localization and functional studies. Here, we utilized this robust and rapid combined ISH/IHC assay to study a subset of commonly highlighted miRNAs including tumor suppressive miRNAs (let-7 and miR-34) and oncogenic miRNAs (miR-21 and miR-155) in a panel of breast, colon, lung, pancreas and prostate carcinomas, which collectively are the leading causes of cancer-related mortality in the United States. Despite the idiosyncrasies of each particular cancer type, general trends emerged that pinpointed to distinct cellular sources of altered miRNA expression. While altered expression of miR-21 and miR-34 was manifested within cancer cells, that of miR-126 and miR-155 was predominantly confined to endothelial cells and immune cells, respectively. These findings suggest a heterogeneous and complex participation of miRNAs in carcinogenesis occurring through cancer cell-autonomous effects as well as through the modulation of stromal, vascular and immune responses. We discuss potential applications of miRNA-based ISH/IHC assays as novel diagnostic and prognostic tools, as well as clinical implications of our findings for miRNA-based therapeutic strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-360.