Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder

TY - JOUR

T1 - Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder

AU - Dohn, Line Hammer

AU - Illemann, Martin

AU - Høyer-Hansen, Gunilla

AU - Christensen, Ib J

AU - Hostmark, Jens

AU - Litlekalsoy, Jorunn

AU - von der Maase, Hans

AU - Pappot, Helle

AU - Laerum, Ole D

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/4

Y1 - 2015/4

N2 - OBJECTIVES: To evaluate the expression-and localization pattern of the urokinase-type plasminogen activator receptor (uPAR), focusing on its clinical implications in patients with urothelial neoplasia of the bladder treated with radical cystectomy. uPAR is a central molecule in tissue remodeling during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia.MATERIALS AND METHODS: The expression-and localization pattern of uPAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages, and myofibroblasts at the invasive front and tumor core, respectively. Statistical analyses were performed to evaluate the association of uPAR localization and score with clinicopathologic covariates and survival.RESULTS: uPAR positivity was seen in 122/137 (89%) and 118/149 (74%) of the neoplasias at the invasive front and tumor core, respectively. uPAR was primarily expressed by myofibroblasts and macrophages in the surrounding stroma as well as some cancer cells. A significant association between uPAR positivity and T-stage as well as grade was found for all 3 cell types in tumor core (P ≤ 0.04 for all comparisons). In univariate analysis, the uPAR positive group had a shorter survival than the uPAR negative group (hazard ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020).CONCLUSIONS: The expression of uPAR is a possible prognostic marker that could be useful in identification of patients with aggressive, highly invasive tumors that could benefit from additional chemotherapy or more intensive follow-up after cystectomy.

AB - OBJECTIVES: To evaluate the expression-and localization pattern of the urokinase-type plasminogen activator receptor (uPAR), focusing on its clinical implications in patients with urothelial neoplasia of the bladder treated with radical cystectomy. uPAR is a central molecule in tissue remodeling during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia.MATERIALS AND METHODS: The expression-and localization pattern of uPAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages, and myofibroblasts at the invasive front and tumor core, respectively. Statistical analyses were performed to evaluate the association of uPAR localization and score with clinicopathologic covariates and survival.RESULTS: uPAR positivity was seen in 122/137 (89%) and 118/149 (74%) of the neoplasias at the invasive front and tumor core, respectively. uPAR was primarily expressed by myofibroblasts and macrophages in the surrounding stroma as well as some cancer cells. A significant association between uPAR positivity and T-stage as well as grade was found for all 3 cell types in tumor core (P ≤ 0.04 for all comparisons). In univariate analysis, the uPAR positive group had a shorter survival than the uPAR negative group (hazard ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020).CONCLUSIONS: The expression of uPAR is a possible prognostic marker that could be useful in identification of patients with aggressive, highly invasive tumors that could benefit from additional chemotherapy or more intensive follow-up after cystectomy.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor

KW - Carcinoma, Transitional Cell

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Neoplasm Staging

KW - Prognosis

KW - Proportional Hazards Models

KW - Receptors, Urokinase Plasminogen Activator

KW - Urinary Bladder Neoplasms

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.urolonc.2014.12.001

DO - 10.1016/j.urolonc.2014.12.001

M3 - Journal article

C2 - 25575713

SN - 1078-1439

VL - 33

SP - 165.e15-24

JO - Urologic Oncology: Seminars and Original Investigations

JF - Urologic Oncology: Seminars and Original Investigations

IS - 4

ER -