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Open Access Research article

Expression of uPAR in tumor-associated stromal cells is associated with colorectal cancer patient prognosis: a TMA study

Martin C Boonstra1, Floris PR Verbeek1, Andrew P Mazar2, Hendrica AJM Prevoo1, Peter JK Kuppen1, Cornelis JH van de Velde1, Alexander L Vahrmeijer1 and Cornelis FM Sier13*

Author Affiliations

1 Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands

2 Chemistry of Life Processes Institute and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL, USA

3 Antibodies for Research Applications BV, Gouda, The Netherlands

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BMC Cancer 2014, 14:269  doi:10.1186/1471-2407-14-269

Published: 17 April 2014

Abstract

Background

The receptor for urokinase-type plasminogen activator (uPAR) is associated with cancer development and progression. Within the tumor microenvironment uPAR is expressed by malignant cells as well as tumor-associated stromal cells. However, the contribution of uPAR expression in these stromal cells to malignancy and patient survival in colorectal cancer is still unclear. This study compares the association of uPAR expression in both colorectal tumor-associated stromal cells and neoplastic cells with clinico-pathological characteristics and patient survival using tissue micro arrays (TMA).

Methods

Immunohistochemical staining of uPAR expression was performed on tumor tissue from 262 colorectal cancer patients. Kaplan-Meier, log rank, and uni- and multivariate Cox’s regression analyses were used to calculate associations between uPAR expression and patient survival.

Results

In the colorectal tumor-associated stromal microenvironment, uPAR is expressed in macrophages, (neoangiogenic) endothelial cells and myofibroblasts. uPAR expression in tumor-associated stromal cells and neoplastic cells (and both combined) were negatively associated with overall survival (OS) and Disease Free Survival (DFS). Uni- and multivariate Cox’s regression analysis for combined uPAR expression in tumor-associated stromal and neoplastic cells showed significant and independent negative associations with OS and DFS. Only uPAR expression in tumor-associated stromal cells showed independent significance in the uni- and multivariate analysis for DFS.

Conclusion

This study demonstrates a significant independent negative association between colorectal cancer patient survival and uPAR expression in especially tumor-associated stromal cells.

Keywords:
Urokinase receptor; Immunohistochemistry; Diagnosis; Survival; Tumor associated stromal cell; Macrophage