title: Prognostic significance of metastasis-related microRNAs in early breast cancer patients with a long follow-up.
abstract: BACKGROUND
  Stability of microRNAs (miRNAs) in formalin-fixed paraffin-embedded (FFPE) tissues enables their reliable analysis in archived FFPE tissue samples, which are an invaluable source for the evaluation of novel biomarkers. Especially in breast cancer, for which late relapses occur in many cases, analysis of miRNAs in FFPE tissues holds great potential, because it can lead to the discovery of novel biomarkers suitable for future routine clinical diagnostics for breast cancer. We investigated the prognostic significance of 6 metastasis-related miRNAs that can critically regulate various stages of migration and invasion and play critical roles in the multistep metastatic process.
  
  
  METHODS
  We quantified the expression of 6 mature miRNAs (namely miR-21, miR-205, miR-10b, miR-210, miR-335, and let-7a) by reverse-transcription quantitative PCR in FFPE tissues of 84 patients with early breast cancer and a long follow-up and 13 cancer-free breast tissue FFPE samples that were used as the control group. We further correlated individual miRNA over- or underexpression with the disease-free interval (DFI) and overall survival (OS).
  
  
  RESULTS
  Univariate analysis revealed that both miR-21 and miR-205 were significantly associated with DFI and only miR-205 with OS. Multivariate analysis demonstrated that miR-205 and miR-21 were independent factors associated with early disease relapse, whereas only miR-205 overexpression was associated with OS.
  
  
  CONCLUSIONS
  Our results clearly indicate that deregulation of metastasis-associated miRNAs in primary tumors is associated with clinical outcome in patients with early breast cancer and can differentiate patients with higher risk in well-characterized subgroups.
authors.affiliation: Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece;
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
authors.forename: Efstathios
authors.initials: E
authors.lastname: Stathopoulos
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Evi
authors.initials: E
authors.lastname: Lianidou
mesh_terms: D001943:Breast Neoplasms / Q000097:blood* / Q000503:physiopathology; D018572:Disease-Free Survival; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs