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

TY - JOUR

T1 - High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer

AU - Rask, Lene

AU - Balslev, Eva

AU - Jørgensen, Stine

AU - Eriksen, Jens

AU - Flyger, Henrik

AU - Møller, Søren

AU - Høgdall, Estrid

AU - Litman, Thomas

AU - Nielsen, Boye Schnack

N1 - © 2011 The Authors. APMIS © 2011 APMIS.

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Breast Neoplasms

KW - Carcinoma, Ductal, Breast

KW - Cell Growth Processes

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization

KW - Ki-67 Antigen

KW - MicroRNAs

KW - Middle Aged

KW - Statistics, Nonparametric

KW - Tumor Markers, Biological

KW - Tumor Suppressor Protein p53

U2 - 10.1111/j.1600-0463.2011.02782.x

DO - 10.1111/j.1600-0463.2011.02782.x

M3 - Journal article

C2 - 21917003

SN - 0903-465X

VL - 119

SP - 663

EP - 673

JO - APMIS. Supplementum

JF - APMIS. Supplementum

IS - 10

ER -