Abstract
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.
Highlights
Esophageal carcinoma is one of most common malignant tumors in the world
We found that M2 macrophages were primarily located in the tumor stroma, but a small number of M2 macrophages reside in tumor islets
To explore the role of M2 macrophages in progression of Kazakh esophageal squamous cell carcinoma (ESCC), we divided the cases into high and low density of M2 macrophage groups according to the median value of CD163-positive macrophages (15 for tumor islet and 58 for tumor stroma), and evaluated possible correlations between M2 macrophages density and Kazakh clinicopathological parameters, including age, gender, tumor location, histological grade, invasion depth, nodal status, and clinical stages, found the increased number of M2 macrophages in tumor stroma were significantly correlated with more malignant phenotypes of Kazakh ESCCs, including lymph node metastasis and clinical stage progression
Summary
Esophageal carcinoma is one of most common malignant tumors in the world. According to its etiological and pathological characteristics, it is divided into two main forms: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. More than 90% of esophageal cancers are classified as ESCCs in China [1]. The Kazakh national minority (ethnic) living in Xinjiang (northwest of China) is a demographic with one of the highest rates of esophageal carcinoma incidence and mortality in China [2]. The 5-year survival rate of esophageal carcinoma is only 10%. Primary reasons for poor prognosis are associated with early stage cancer cell invasion and high metastasis [3]
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