title: High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer.
abstract: Low-risk and high-risk breast cancer patients are stratified primarily according to their lymph node (LN) status and grading. However, some low-risk patients relapse, and some high-risk patients have a favorable clinical outcome, implying a need for better prognostic and predictive tests. Micro RNAs are often aberrantly expressed in cancer and microRNA-21 is upregulated in a variety of cancers, including breast cancer. High miR-21 levels have been associated with poor prognosis. To determine the cellular localization of miR-21 and to compare its expression levels with histopathological features, we performed in situ hybridization and semi-quantitative assessment of the miR-21 signal on 12 LN negative grade I (assumed low risk), and 12 LN positive grade II (high risk) breast cancers. miR-21 was predominantly seen in cancer associated fibroblast-like cells, with no difference in expression levels between grade I and grade II carcinomas. Immunohistochemical scoring of the prognostic proliferation marker Ki-67 and tumor suppressor p53 showed that the miR-21 expression levels significantly correlated with the Ki-67 score (p = 0.043), whereas no correlation between p53 and miR-21 was found. Our results indicate that miR-21 may contribute to improve clinical stratification according to growth rate and facilitate tailored treatment of breast cancer patients.
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark. lenras05@heh.regionh.dk
authors.forename: Lene
authors.initials: L
authors.lastname: Rask
authors.forename: Eva
authors.initials: E
authors.lastname: Balslev
authors.forename: Stine
authors.initials: S
authors.lastname: Jørgensen
authors.forename: Jens
authors.initials: J
authors.lastname: Eriksen
authors.forename: Henrik
authors.initials: H
authors.lastname: Flyger
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D048708:Cell Growth Processes / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D018709:Statistics, Nonparametric; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53