Prognostic significance of CD204-positive macrophages in upper urinary tract cancer.
BACKGROUND
Evidence suggests that CD204-positive (CD204(+)) tumor-infiltrating macrophages are associated with aggressive behavior of various cancers; however, the clinical, pathological, and prognostic associations of tumor-infiltrating CD204(+) macrophages in urothelial cancer have not been reported.


METHODS
A tissue microarray was constructed from the centers and peripheries of 171 upper urinary tract cancers treated with nephroureterectomy. CD204 immunohistochemistry was performed. The density of CD204(+) cells was calculated using image analysis software, and survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional hazards regression models.


RESULTS
High CD204(+) cell density at the centers and peripheries of tumors was significantly associated with several adverse prognostic factors, including sessile architecture, histological high-grade, presence of lymphovascular invasion, concomitant carcinoma in situ, higher tumor stage, and lymph node metastasis. High CD204(+) cell density was significantly associated with shorter metastasis-free and cancer-specific survival (log-rank p < 0.001) and shorter metastasis-free survival in multivariate analysis.


CONCLUSIONS
A high density of tumor-infiltrating CD204(+) macrophages was associated with aggressive behavior of upper urinary tract cancer. Our results suggest that a specific immune microenvironment may be associated with the biological behavior of urothelial cancer and that CD204 may serve as a novel prognostic biomarker for these tumors.
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takashi
T
Ichimura
Teppei
T
Morikawa
Taketo
T
Kawai
Tohru
T
Nakagawa
Hirokazu
H
Matsushita
Kazuhiro
K
Kakimi
Haruki
H
Kume
Shumpei
S
Ishikawa
Yukio
Y
Homma
Masashi
M
Fukayama
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000737:chemistry*; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D051117:Scavenger Receptors, Class A / Q000032:analysis*; D015996:Survival Rate; D046888:Tissue Array Analysis; D014516:Ureteral Neoplasms / Q000473:pathology* / Q000601:surgery
D014408:Biomarkers, Tumor; C495139:MSR1 protein, human; D051117:Scavenger Receptors, Class A