High CD204+ tumor-infiltrating macrophage density predicts a poor prognosis in patients with urothelial cell carcinoma of the bladder
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Bo Wang1,2,*, Hao Liu2,*, Xiaoliang Dong1,*, Shaoxu Wu2, Hong Zeng3, Zhuowei Liu4, Di Wan2, Wen Dong2, Wang He2, Xu Chen2, Limin Zheng5, Jian Huang2, Tianxin Lin1,2
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, PR China
2Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China
3Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhongshan) University, Guangzhou, PR China
4Department of Urology, Cancer Center, Sun Yat-Sen (Zhongshan) University, Guangzhou, PR China
5State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen (Zhongshan) University, Guangzhou, PR China
*These authors have contributed equally to this work
Tianxin Lin, e-mail: [email protected]
Jian Huang, e-mail: [email protected]
Keywords: tumor-infiltrating macrophages, CD204, CD169, urothelial cell carcinoma of the bladder (UCB)
Received: December 03, 2014 Accepted: April 25, 2015 Published: May 07, 2015
Macrophages (Mφs) are a major cell type that can infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. This study attempted to investigate the prognostic values of various tumor-infiltrating Mφ phenotypes in patients with urothelial cell carcinoma of the bladder (UCB), with a focus on Mφ tissue microlocalization. Mφs were assessed by immunohistochemistry in tissues from 302 UCB patients using CD68 as a pan-Mφ marker, and CD204 and CD169 as robust pro- and anti-tumoral Mφ phenotype markers, respectively. Our data showed that these Mφ phenotypes were predominately distributed in stromal (ST) rather than in intratumoral (INT) regions (all P < 0.0001). Surprisingly, CD204 and CD169 can be co-expressed by the same CD68+ Mφs. Kaplan-Meier analysis revealed that all INT- and ST-infiltrating CD204+ or CD169+ Mφ densities were inversely associated with overall survival (all P < 0.01). By multivariate analysis, ST-infiltrating CD204+ Mφ density emerged as an independent prognostic factor for overall survival (HR, 1.981; P = 0.022). Moreover, the density of ST-infiltrating CD204+ Mφs was positively associated with the tumor size (P = 0.001), tumor stage (P < 0.0001), nodal metastasis (P < 0.0001), and histological grade (P < 0.0001). Our findings suggest that CD204+ Mφs might play detrimental protumoral roles and represent the predominant Mφ phenotype in human bladder cancer.
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