title: Validation of expression patterns for nine miRNAs in 204 lymph-node negative breast cancers.
abstract: BACKGROUND
  Although lymph node negative (LN-) breast cancer patients have a good 10-years survival (∼85%), most of them still receive adjuvant therapy, while only some benefit from this. More accurate prognostication of LN- breast cancer patient may reduce over- and under-treatment. Until now proliferation is the strongest prognostic factor for LN- breast cancer patients. The small molecule microRNA (miRNA) has opened a new window for prognostic markers, therapeutic targets and/or therapeutic components. Previously it has been shown that miR-18a/b, miR-25, miR-29c and miR-106b correlate to high proliferation.
  
  
  METHODS
  The current study validates nine miRNAs (miR-18a/b miR-25, miR-29c, miR-106b, miR375, miR-424, miR-505 and let-7b) significantly correlated with established prognostic breast cancer biomarkers. Total RNA was isolated from 204 formaldehyde-fixed paraffin embedded (FFPE) LN- breast cancers and analyzed with quantitative real-time Polymerase Chain Reaction (qPCR). Independent T-test was used to detect significant correlation between miRNA expression level and the different clinicopathological features for breast cancer.
  
  
  RESULTS
  Strong and significant associations were observed for high expression of miR-18a/b, miR-106b, miR-25 and miR-505 to high proliferation, oestrogen receptor negativity and cytokeratin 5/6 positivity. High expression of let-7b, miR-29c and miR-375 was detected in more differentiated tumours. Kaplan-Meier survival analysis showed that patients with high miR-106b expression had an 81% survival rate vs. 95% (P = 0.004) for patients with low expression.
  
  
  CONCLUSIONS
  High expression of miR-18a/b are strongly associated with basal-like breast cancer features, while miR-106b can identify a group with higher risk for developing distant metastases in the subgroup of Her2 negatives. Furthermore miR-106b can identify a group of patients with 100% survival within the otherwise considered high risk group of patients with high proliferation. Using miR-106b as a biomarker in conjunction to mitotic activity index could thereby possibly save 18% of the patients with high proliferation from overtreatment.
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Jonsdottir
authors.forename: Susanne R
authors.initials: SR
authors.lastname: Janssen
authors.forename: Fabiana C
authors.initials: FC
authors.lastname: Da Rosa
authors.forename: Einar
authors.initials: E
authors.lastname: Gudlaugsson
authors.forename: Ivar
authors.initials: I
authors.lastname: Skaland
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C542541:MIRN106 microRNA, human; C543351:MIRN25 microRNA, human; C532045:MIRN29a microRNA, human; C554214:MIRN424 microrna, human; C574053:MIRN505 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D011960:Receptors, Estrogen; C487931:mirnlet7 microRNA, human