High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer

Authors


  • Present 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

Lene Rask, Department of Oncology 54O5, Herlev Hospital, 2730 Herlev, Denmark. e-mail: lenras05@heh.regionh.dk

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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