title: The microRNA maturation regulator Drosha is an independent predictor of outcome in breast cancer patients.
abstract: Drosha is a protein that plays a key role in the biogenesis of microRNAs which are well known to be deranged in human breast cancer (BC). The purpose of the current study was to assess the biological and prognostic value of Drosha protein expression in BC. Drosha protein expression was assessed immunohistochemically in two sets of BC: (1) full-face sections of selected BC series with distinct stages of tumour progression (Normal parenchymal cells, ductal carcinoma in situ (DCIS), primary invasive BC and nodal metastases) to evaluate its differential expression, (2) tissue microarray comprising a large and well-characterised series of unselected clinically annotated invasive BC to investigate its correlation with clinicopathological features and patient outcome. A gradual loss of Drosha cytoplasmic expression was observed along tumour progression from DCIS, to invasive and to metastatic cancer cells. In invasive BC, loss of Drosha cytoplasmic expression was associated with BRCA1 and ER expression and with shorter BC specific survival (BCSS), disease free interval (DFI) and distant metastasis free interval (DMFI). This correlation was maintained in ER negative, HER2 negative, triple negative and LN negative cases. Moreover, loss of cytoplasmic Drosha was predictive of better response to chemotherapy and endocrine therapy. This study provides evidence that Drosha protein potentially plays an important role in BC progression and assessment of its expression provides an independent predictor of patient outcome. These observations provide further evidence that alterations in miRNA regulation influence tumour behaviour.
authors.affiliation: Department of Histopathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, UK. mrxsmok8@nottingham.ac.uk
authors.forename: Sarkawt M
authors.initials: SM
authors.lastname: Khoshnaw
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.forename: Tarek
authors.initials: T
authors.lastname: Abdel-Fatah
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nolan
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Hodi
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Macmillan
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D043244:Ribonuclease III / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: C517918:DROSHA protein, human; D043244:Ribonuclease III