title: Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer.
abstract: Inflammation is an important feature of carcinogenesis. Tumor-associated macrophages (TAMs) can be associated with either poor or improved prognosis, depending on their properties and polarization. Current knowledge of the prognostic significance of TAMs in bladder cancer is limited and was investigated in this study. We analyzed 184 urothelial bladder cancer patients undergoing transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan-macrophage marker), MAC387 (polarized towards type 1 macrophages), and CLEVER-1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels) were detected immunohistochemically. The median follow-up time was 6.0 years. High macrophage counts associated with a higher pT category and grade. Among patients undergoing transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were associated with increased risk of progression and poorer disease-specific and overall survival in univariate analyses. High levels of two macrophage markers (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups) had an independent prognostic role after transurethral resection in multivariate analyses. In the cystectomy cohort, MAC387, alone and in combination with CD68, was associated with poorer survival in univariate analyses, but none of the markers were independent predictors of outcome in multivariate analyses. In conclusion, this study demonstrates that macrophage phenotypes provide significant independent prognostic information, particularly in bladder cancers undergoing transurethral resection.
authors.affiliation: MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Minna M
authors.initials: MM
authors.lastname: Boström
authors.affiliation: MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland; Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital, Turku, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Irjala
authors.affiliation: Department of Pathology, Helsinki University Hospital (HUSLAB) and Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Mirtti
authors.affiliation: Department of Pathology, Turku University Hospital, Turku, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Taimen
authors.affiliation: Department of Biostatistics, University of Turku, Turku, Finland.
authors.forename: Tommi
authors.initials: T
authors.lastname: Kauko
authors.affiliation: MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland; Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
authors.forename: Annika
authors.initials: A
authors.lastname: Ålgars
authors.affiliation: MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Department of Urology, Turku University Hospital, Turku, Finland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Boström
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001500:BCG Vaccine / Q000737:chemistry; D040502:Calgranulin B / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D015331:Cohort Studies; D015653:Cystectomy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001500:BCG Vaccine; D040502:Calgranulin B; D015816:Cell Adhesion Molecules, Neuronal; D016201:Receptors, Lymphocyte Homing; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C449926:STAB1 protein, human