title: Epithelial and stromal cell urokinase plasminogen activator receptor expression differentially correlates with survival in rectal cancer stages B and C patients.
abstract: Urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for colorectal cancer (CRC) patient survival. However, CRC uPAR expression remains controversial, especially regarding cell types where uPAR is overexpressed (e.g., epithelium (uPARE) or stroma-associated cells (uPARS)) and associated prognostic relevance. In this study, two epitope-specific anti-uPAR monoclonal antibodies (MAbs) could discriminate expression of uPARE from uPARS and were used to examine this association with survival of stages B and C rectal cancer (RC) patients. Using immunohistochemistry, MAbs #3937 and R4 were used to discriminate uPARE from uPARS respectively in the central and invasive frontal regions of 170 stage B and 179 stage C RC specimens. Kaplan-Meier and Cox regression analyses were used to determine association with survival. uPAR expression occurred in both epithelial and stromal compartments with differential expression observed in many cases, indicating uPARE and uPARS have different cellular roles. In the central and invasive frontal regions, uPARE was adversely associated with overall stage B survival (HR = 1.9; p = 0.014 and HR = 1.5; p = 0.031, respectively) reproducing results from previous studies. uPARS at the invasive front was associated with longer stage C survival (HR = 0.6; p = 0.007), reflecting studies demonstrating that macrophage peritumoural accumulation is associated with longer survival. This study demonstrates that different uPAR epitopes should be considered as being expressed on different cell types during tumour progression and at different stages in RC. Understanding how uPARE and uPARS expression affects survival is anticipated to be a useful clinical prognostic marker of stages B and C RC.
authors.affiliation: Australian School of Advanced Medicine, Faculty of Human Science, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Seong Beom
authors.initials: SB
authors.lastname: Ahn
authors.affiliation: Anatomical Pathology Department, Concord Hospital and Discipline of Pathology, University of Sydney, Concord, NSW 2139, Australia.
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.affiliation: Department of Colorectal Surgery, Concord Hospital and Discipline of Surgery, University of Sydney, Concord, NSW 2139, Australia.
authors.forename: Owen F
authors.initials: OF
authors.lastname: Dent
authors.affiliation: Australian School of Advanced Medicine, Faculty of Human Science, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Abidali
authors.initials: A
authors.lastname: Mohamedali
authors.affiliation: Anatomical Pathology Department, Concord Hospital and Discipline of Pathology, University of Sydney, Concord, NSW 2139, Australia.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kwun
authors.affiliation: Anatomical Pathology Department, Concord Hospital and Discipline of Pathology, University of Sydney, Concord, NSW 2139, Australia.
authors.forename: Candice
authors.initials: C
authors.lastname: Clarke
authors.affiliation: Anatomical Pathology Department, Concord Hospital and Discipline of Pathology, University of Sydney, Concord, NSW 2139, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Fletcher
authors.affiliation: Department of Colorectal Surgery, Concord Hospital and Discipline of Surgery, University of Sydney, Concord, NSW 2139, Australia.
authors.forename: Pierre H
authors.initials: PH
authors.lastname: Chapuis
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Edouard C
authors.initials: EC
authors.lastname: Nice
authors.affiliation: Australian School of Advanced Medicine, Faculty of Human Science, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D017154:Stromal Cells / Q000378:metabolism; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator