title: Biological and prognostic associations of miR-205 and let-7b in breast cancer revealed by in situ hybridization analysis of micro-RNA expression in arrays of archival tumour tissue.
abstract: Micro-RNAs (miRNAs) are frequently dysregulated in a range of human malignancies, many have been shown to act either as tumour supressors or oncogenes and several have been implicated in breast cancer. However, breast cancer is a diverse disease and little is known about the relationships between miRNA expression, clinical outcome and tumour subtype. We used locked nucleic acid probe in situ hybridization (LNA-ISH) to visualize, in tissue micro-arrays (TMAs) of 2919 formalin-fixed paraffin-embedded (FFPE) archival breast tumours, the expression of two key miRNAs that are frequently lost in a range of solid malignancies, let-7b and miR-205. These miRNAs were also quantified by quantitative reverse transcription PCR in cores of FFPE tissue from 40 of these cases, demonstrating that LNA-ISH is semi-quantitative. The tumours in the TMAs were assigned to subtypes based on their immunohistochemical (IHC) staining with ER, PR, HER2, CK5/6 and EGFR. let-7b expression was shown to be associated with luminal tumours and to have an independent significant positive prognostic value in this group. miR-205 is associated with tumours of ductal morphology and is of significant positive prognostic value within these tumours. We propose that the expression of miR-205 may contribute to ductal tumour morphology.
authors.affiliation: Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, UK. John.LeQuesne@cancer.org.uk
authors.forename: John Le
authors.initials: JL
authors.lastname: Quesne
authors.forename: Julia
authors.initials: J
authors.lastname: Jones
authors.forename: Joanna
authors.initials: J
authors.lastname: Warren
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Dawson
authors.forename: H Raza
authors.initials: HR
authors.lastname: Ali
authors.forename: Helen
authors.initials: H
authors.lastname: Bardwell
authors.forename: Fiona
authors.initials: F
authors.lastname: Blows
authors.forename: Paul
authors.initials: P
authors.lastname: Pharoah
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D016009:Chi-Square Distribution; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000032:analysis*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016707:Tissue Fixation / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D005404:Fixatives; D005557:Formaldehyde; D035683:MicroRNAs; C534425:MIR205, human; C487931:mirnlet7 microRNA, human