Abstract

Abstract In order to detect early pathological changes in breast tissue, which could reveal the underlying mechanism to cancer progression, we investigated the microRNA (miRNA) expression profile in hyperplastic enlarged lobular units (HELUs). HELUs arise from normal terminal duct lobular units (TDLUs) and are potentially the earliest histologically identifiable alterations in the development of breast cancer. TDLUs and HELUs, from formalin-fixed paraffin embedded tissue from patients with high risk of developing breast cancer, were laser capture microdissected and the RNA was extracted. Expression profiles were obtained using a qRT-PCR-based array analyzing 667 human miRNAs. In the first set of miRNA array analyses of paired samples from four specimens with early HELUs, we obtained a list of 16 downregulated and 10 upregulated miRNAs with a significant change (p<0.05) in expression. Among the most pronounced altered miRNAs were miR-136, miR-301b, miR-302b and miR-576-5p. To validate these results, more paired samples of fully developed HELUs will be added to the study and candidate miRNAs will be further validated using qPCR and in situ hybridization of formalin fixed specimens using a selection material of 100 patients with high risk of breast cancer. These ongoing miRNA analyses will potentially reveal additional miRNAs that are linked to the development of TDLUs towards HELUs as well as substantiating the frequency of the various alterations observed. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2077.

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