Research Papers:

CD163 as a marker of M2 macrophage, contribute to predict aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma

Jian Ming Hu, Kai Liu, Ji Hong Liu, Xian Li Jiang, Xue Li Wang, Yun Zhao Chen, Shu Gang Li, Hong Zou, Li Juan Pang, Chun Xia Liu, Xiao Bin Cui, Lan Yang, Jin Zhao, Xi Hua Shen, Jin Fang Jiang, Wei Hua Liang, Xiang Lin Yuan and Feng Li _

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Oncotarget. 2017; 8:21526-21538. https://doi.org/10.18632/oncotarget.15630

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Jian Ming Hu1,3, Kai Liu1, Ji Hong Liu1, Xian Li Jiang1, Xue Li Wang1, Yun Zhao Chen1, Shu Gang Li4, Hong Zou1, Li Juan Pang1, Chun Xia Liu1, Xiao Bin Cui1, Lan Yang1, Jin Zhao1, Xi Hua Shen1, Jin Fang Jiang1, Wei Hua Liang1, Xiang Lin Yuan3, Feng Li1,2

1Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832003, China

2Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China

3Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

4Department of Preventive Medicine, Shihezi University School of Medicine, Shihezi, 832003, China

Correspondence to:

Feng Li, email: [email protected]

Keywords: Kazakh, esophageal squamous cell carcinoma, macrophage, CD163, MMP9

Received: November 18, 2016     Accepted: February 07, 2017     Published: February 22, 2017


M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of esophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.

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