Abstract
BackgroundThe 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).MethodsImmunohistochemical 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.ResultsIn 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.ConclusionThis study demonstrates a significant independent negative association between colorectal cancer patient survival and uPAR expression in especially tumor-associated stromal cells.
Highlights
The incidence of colorectal cancer is varying worldwide, in the western world it is the third most frequent cancer type [1]
No correlation was found between urokinase-type plasminogen activator (uPAR) expression on neoplastic cells and tumor-associated stromal cells (p = 0.063)
This study demonstrates the relationship between enhanced expression of the urokinase receptor in colorectal tumor-associated stromal cells and a significant worse patient survival
Summary
The incidence of colorectal cancer is varying worldwide, in the western world it is the third most frequent cancer type [1]. Primarily the anatomic extent of the tumor is used to predict patient prognosis and select optimal treatment strategies. The receptor for urokinase-type plasminogen activator (uPAR) is associated with cancer development and progression. 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). In various cancer types, enhanced expression of uPAR is associated with worse patient prognosis and survival.
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