Abstract P3-09-06: microRNA Signature of Columnar Cell Hyperplasia from Patients with High Risk of Breast Cancer

Abstract

Abstract Background: Columnar cell hyperplasia (CCH) is considered to originate in normal terminal duct lobular units (TDLUs) and is potentially the first histologically identifiable alteration in the development of breast cancer. 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 TDLUs and CCH. Material and Methods: Epithelial cells and surrounding stroma of TDLUs and CCH from formalin-fixed paraffin embedded tissue (FFPE) from patients with high risk of developing breast cancer were laser capture microdissected and RNA was extracted. MiRNA expression profiles were obtained using a qRT-PCR-based array analyzing 667 human miRNAs. Results: Increased levels of ERα were present in the epithelial cells of CCH as previously reported. Immunohistochemical staining for the stromal activation marker smooth muscle actin (SMA) was negative in fibroblasts surrounding both TDLUs and CCH, suggesting lack of major activation of the stroma. Interestingly, array analysis revealed changes in miRNA expression pattern in both epithelial and stromal compartments. Correlation analyses of the array results indicated a high reproducibility (r2:0.82-0.94) supporting stable miRNA profiles in TDLUa and CCH. MiRNA array analysis of paired samples from specimens with both TDLUs and CCH resulted in significant (P<0.05) decreased levels of 15 miRNAs in epithelial cells of CCH and downregulation of 18 miRNAs in the stroma. Examples of altered miRNAs in the epithelial cells are miR-532-3p, miR-886-3p, let-7c, miR-491-5p, miR-365, and example miRNAs in the stroma are miR-195, miR-99a, miR-224, miR-19b, miR-423-5p. Further validation of a selection of miRNAs in a patient material using in situ hybridization is currently being performed to verify the array results. Discussion: This data will potentially link these miRNAs to the development of TDLUs towards CCH and possibly lead to the discovery of new markers for precancerous conditions and potentially new therapeutic targets. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-09-06.