High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer
LENE RASK
Department of Oncology, Herlev Hospital, University of Copenhagen
Faculty of Health Sciences, University of Copenhagen
Search for more papers by this authorEVA BALSLEV
Department of Pathology, Herlev Hospital, University of Copenhagen
Search for more papers by this authorHENRIK FLYGER
Department of Breast Surgery, Herlev Hospital, University of Copenhagen, Denmark
Search for more papers by this authorESTRID HØGDALL
Department of Pathology, Herlev Hospital, University of Copenhagen
Search for more papers by this authorLENE RASK
Department of Oncology, Herlev Hospital, University of Copenhagen
Faculty of Health Sciences, University of Copenhagen
Search for more papers by this authorEVA BALSLEV
Department of Pathology, Herlev Hospital, University of Copenhagen
Search for more papers by this authorHENRIK FLYGER
Department of Breast Surgery, Herlev Hospital, University of Copenhagen, Denmark
Search for more papers by this authorESTRID HØGDALL
Department of Pathology, Herlev Hospital, University of Copenhagen
Search for more papers by this authorPresent address: Søren Møller, Novozymes A/S, Krogshoejvej 36, DK-2880 Bagsvaerd; Thomas Litman, Department of International Health, Immunology and Microbiology, Faculty Of Health Sciences, University of Copenhagen; Boye Schnack Nielsen, Bioneer A/S, DK-2970 Hørsholm, Denmark
Abstract
Rask L, Balslev E, Jørgensen S, Eriksen J, Flyger H, Møller S, Høgdall E, Litman T, Nielsen BS. High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer. APMIS 2011; 119: 663–73.
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.
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