Intratumoral and peritumoral expression of CD68 and CD206 in hepatocellular carcinoma and their prognostic value

Ren,Chun-Xia; Leng,Rui-Xue; Fan,Yin-Guang; Pan,Hai-Feng; Li,Bao-Zhu; Wu,Chang-Hao; Wu,Qiang; Wang,Na-Na; Xiong,Qi-Ru; Geng,Xiao-Ping; Ye,Dong-Qing

doi:10.3892/or.2017.5738

Intratumoral and peritumoral expression of CD68 and CD206 in hepatocellular carcinoma and their prognostic value

Authors:
- Chun-Xia Ren
- Rui-Xue Leng
- Yin-Guang Fan
- Hai-Feng Pan
- Bao-Zhu Li
- Chang-Hao Wu
- Qiang Wu
- Na-Na Wang
- Qi-Ru Xiong
- Xiao-Ping Geng
- Dong-Qing Ye
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Affiliations: Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, P.R. China, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK, Pathology Center, Department of Pathology, Anhui Medical University, Hefei, Anhui, P.R. China, General Department of Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
Published online on: June 21, 2017 https://doi.org/10.3892/or.2017.5738
Pages: 886-898
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aims of the present study were to determine whether the changes in density and location of CD68-positive and CD206-positive macrophages contribute to progression of hepatocellular carcinoma (HCC) and to evaluate prognostic values of these cells in post-surgical patients. A retrospective study involving 268 HCC patients was conducted. CD68-positive and CD206-positive macrophage infiltration in HCC tissues and adjacent tissues was examined by immunohistochemistry (IHC) and the relationship between the clinicopathological features and prognosis was analyzed. Receiver operating characteristics (ROC) curve was used to calculate diagnostic accuracy. There was an increase in CD68-positive and CD206-positive macrophage infiltration in adjacent tumor tissues compared with tumor tissues. ROC curve identified their optimal diagnostic cut-off values. The survival analysis showed that increased CD68 expression in adjacent tissues conferred superior overall survival (OS) and disease-free survival (DFS), while increase of CD206 in tumor yielded inferior OS and DFS. Cox regression analysis suggested both CD68-positive macrophages in adjacent area and intratumor CD206-positive macrophages as independent prognostic biomarkers for post-surgical HCC patients. Finally, a combination of CD68/CD206 and HBV-positive further improved prognostic stratification, especially in DFS. These results provide the first evidence for region- and subset-dependent involvement of CD68 and CD206 cells in HCC progression. A combination of CD68/CD206 density and HBV-positivity improves further predictive value for post-operative recurrence of HCC. Quantification of CD68/CD206 macrophages and their distribution can be exploited for better postsurgical management of HCC patients. These findings provide a basis for developing novel treatment strategies aimed at re-educating macrophages in tumor microenvironment.

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