title: Down-regulation of the miRNA master regulators Drosha and Dicer is associated with specific subgroups of breast cancer.
abstract: Down-regulation of Drosha and Dicer has been suggested to be of prognostic value in some cancers. The aims of our study were to investigate the down-regulation of Drosha and Dicer in breast cancers and its associations with clinicopathological features, molecular subtypes and outcome. Drosha and Dicer expression was assessed with real-time RT-PCR in 245 patients with breast cancer receiving adjuvant anthracycline-based chemotherapy and compared to expression levels of normal breast tissue. Drosha down-regulation was observed in 18% of cases and was associated with high grade, high Ki-67, lack of Bcl2 expression, HER2 over-expression and gene amplification and TOPO2A gene amplification. Dicer down-regulation was found in 46% of cases and was associated with lack of expression of ER, PR and Bcl2 and with high grade, high Ki-67, triple-negative and basal-like phenotypes. Drosha and Dicer were concurrently down-regulated in 15% of cases and significantly associated with high grade and high Ki-67 index. No significant associations between down-regulation of Drosha and/or Dicer and outcome were observed. Our results suggest that down-regulation of Drosha and/or Dicer is not robustly associated with the outcome of breast cancer patients treated with adjuvant anthracycline-based chemotherapy but preferentially observed in distinct subgroups of breast cancer.
authors.affiliation: Molecular Pathology Laboratory, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Konstantin J
authors.initials: KJ
authors.lastname: Dedes
authors.forename: Rachael
authors.initials: R
authors.lastname: Natrajan
authors.forename: Maryou B
authors.initials: MB
authors.lastname: Lambros
authors.forename: Felipe C
authors.initials: FC
authors.lastname: Geyer
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Lopez-Garcia
authors.forename: Kay
authors.initials: K
authors.lastname: Savage
authors.forename: Robin L
authors.initials: RL
authors.lastname: Jones
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism*
chemical_list: D018943:Anthracyclines; D014408:Biomarkers, Tumor; D035683:MicroRNAs; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases