Genética

Abstract
MicroRNAs (miRNAs) are a new class of short noncoding
regulatory RNAs (18–25 nucleotides) that are involved in
diverse developmental and pathologic processes.Al teredmiRNA expression has been associated with several types of
human cancer.H owever, most studies did not establish
whether miRNA expression changes occurred within cells
undergoingmalignant transformation.T o obtain insight into
miRNA deregulation in breast cancer, we implemented an
in situ hybridization (ISH) method to reveal the spatial
distribution ofmiRNA expression in archived formalin-fixed,
paraffin-embedded specimens representing normal and tumor
tissue from >100 patient cases.Her e, we report that
expression of miR-145 andmiR-205 was restricted to the
myoepithelial/basal cell compartment of normal mammary
ducts and lobules, whereas their accumulation was reduced or
completely eliminated in matchingtumor specimens.Conversely,
expression of other miRNAs was detected at varying
levels predominantly within luminal epithelial cells in normal
tissue; expression of miR-21 wasfrequently increased, whereas
that of let-7a was decreased in malignant cells.W e also
analyzed the association of miRNA expression with that of
epithelial markers; prognosticindicators such as estrogen
receptor, progesterone receptor, and HER2; as well as clinical
outcome data.This ISH approach provides a more direct and
informative assessment of howaltered miRNA expression
contributes to breast carcinogenesis compared with miRNA
expression profiling in gross tissue biopsies.M ost significantly,
early manifestation of alteredmiR-145 expression in atypical
hyperplasia and carcinoma in situ lesions suggests that this
miRNA may have a potential clinical application as a novel
biomarker for early detection.