The CCL2-CCR2 Axis in Lymph Node Metastasis From Oral Squamous Cell Carcinoma: An Immunohistochemical Study
The CCL2-CCR2 Axis in Lymph Node Metastasis From Oral Squamous Cell Carcinoma: An Immunohistochemical Study
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DOI：
10.1016/j.joms.2016.09.052
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发表时间：
2017-04-01
影响因子：
1.9
通讯作者：
Ikeda, Tohru
中科院分区：
文献类型：
--
作者：
Fujita, Shuichi;Ikeda, Tohru
目的：细胞因子或趋化因子网络涉及各种恶性肿瘤的淋巴转移和远处转移，包括口腔鳞状细胞癌（OSCC）。应用免疫组化方法研究CC趋化因子受体2（CCR 2）和CC趋化因子受体2配体（CCL 2）轴在淋巴结转移中的作用，特别是原发性OSCC与区域淋巴结边缘窦组织细胞增生症之间的关系。13例无转移病例，15例原发肿瘤切除时转移病例，13例切除后转移病例进行了检查。无患者在颈淋巴结清扫术前接受放疗或化疗。样本固定在福尔马林中，石蜡包埋，并进行免疫组化分析，使用抗体对CCL 2，CCR 2，podoplanin，和α-平滑肌肌动蛋白（α-SMA）。CCL 2在肿瘤相关中性粒细胞（TAN）中表达，在原发肿瘤部位检测到中分化或低分化SCC。在淋巴结中，表达CCL 2的TAN流入边缘窦。CCR 2阳性巨噬细胞和间充质细胞浸润肿瘤间质，并在癌巢内观察到。它们主要存在于转移病例的边缘窦中。在小的转移灶中，在巨噬细胞旁可见类似于癌相关成纤维细胞（CAFs）的α-SMA阳性梭形细胞。结论：CCL 2-CCR 2轴与淋巴结转移有关。为了阐明口腔鳞癌淋巴道转移的机制，建议对本研究中检测到的CCL 2阳性TANs、CCR 2阳性巨噬细胞和CAF样细胞进行进一步的功能分析。(C)2016年美国口腔颌面外科医师协会
Purpose: Cytokine or chemokine networks involve lymphatic and distant metastasis of various malignancies, including oral squamous cell carcinoma (OSCC). Immunohistochemical analysis was used to investigate the contribution of the axis of the CC chemokine receptor-2 (CCR2) and the CC chemokine receptor-2 ligand (CCL2) to lymphatic metastasis, particularly the relation between primary OSCC and marginal sinus histiocytosis in regional lymph nodes.Materials and Methods: Thirteen metastasis-free cases, 15 metastatic cases at resection of primary tumor resection, and 13 postresection metastasis cases were examined. No patient was treated with radiotherapy or chemotherapy before neck dissection. Samples were fixed in formalin, embedded in paraffin, and subjected to immunohistochemical analysis using antibodies against CCL2, CCR2, podoplanin, and alpha-smooth muscle actin (alpha-SMA).Results: Marginal sinus histiocytosis was frequently observed in metastatic cases. CCL2 was expressed in tumor-associated neutrophils (TANs) and moderately or poorly differentiated SCC was detected at primary tumor sites. TANs expressing CCL2 flowed into the marginal sinus in the lymph nodes. CCR2-positive macrophages and mesenchymal cells infiltrated the tumor stroma and were seen within the carcinoma nests. They were predominantly present in the marginal sinus of metastatic cases. In small metastatic foci, alpha-SMA-positive spindle cells resembling carcinoma-associated fibroblasts (CAFs) were observed adjacent to the macrophages.Conclusion: The CCL2-CCR2 axis is associated with lymphatic metastasis. To clarify the mechanism of lymphatic metastasis from OSCC, further functional analyses of the CCL2-positive TANs, CCR2-positive macrophages, and CAF-like cells detected in this study are recommended. (C) 2016 American Association of Oral and Maxillofacial Surgeons