CCL18在恶性黑素瘤中的表达及其与血管内皮生长因子、Ki67表达的相关性研究

中华皮肤科杂志 ›› 2016, Vol. 49 ›› Issue (10): 688-691.

CCL18在恶性黑素瘤中的表达及其与血管内皮生长因子、Ki67表达的相关性研究

宋昊¹,王白鹤¹,邵雪宝²,程伟³,熊竞舒⁴,王小坡⁴,王建⁴,曾学思²,徐秀莲²,孙建方²

1. 中国医学科学院南京皮肤病研究所
2. 南京中国医学科学院北京协和医学院皮肤病研究所
3. 中国医学科学院皮肤病医院
4. 中国医学科学院北京协和医学院皮肤病研究所

收稿日期:2016-01-29 修回日期:2016-06-17 出版日期:2016-10-15 发布日期:2016-09-30
通讯作者: 徐秀莲 E-mail:xxlqjl@sina.com
基金资助:
国家自然科学基金;江苏省自然科学基金;江苏省自然科学基金

Expression of CC chemokine ligand 18 in cutaneous malignant melanoma tissues and its relationship with vascular endothelial growth factor and Ki67 antigen s

Received:2016-01-29 Revised:2016-06-17 Online:2016-10-15 Published:2016-09-30
Contact: Xiu-Lian Xu E-mail:xxlqjl@sina.com

摘要/Abstract

摘要：

目的探讨趋化因子配体18（CCL18）在恶性黑素瘤（恶黑）组织中的表达和临床意义，与血管内皮生长因子（VEGF）、Ki67表达的相关性。方法用免疫组化方法检测58例恶黑石蜡标本中CCL18、VEGF及细胞增殖核抗原Ki67的表达，同时检测20例色素痣石蜡标本中CCL18的表达水平。对CCL18的表达与恶黑临床病理及VEGF、Ki67的表达进行相关性分析。用免疫荧光方法验证CCL18在恶黑组织中的表达。结果 CCL18在恶黑组阳性率为84.48%（49/58），而在色素痣组均无表达，差异有统计学意义（χ2 = 45.46，P < 0.01）。CCL18在恶黑的表达与肿瘤Clark分级、Breslow厚度呈正相关（rs值分别为0.609、0.644，均P < 0.01）；在有无溃疡以及有无淋巴结转移组间差异有统计学意义（均P < 0.05）。CCL18的表达在不同性别、年龄、肢端/非肢端恶黑患者组间差异无统计学意义（均P > 0.05）。恶黑中CCL18阳性表达水平与VEGF表达水平呈正相关（rs = 0.727， P < 0.05），与Ki67表达水平无相关（P > 0.05）。免疫荧光显示，恶黑组织中肿瘤细胞胞质表达CCL18。结论 CCL18在恶黑组织中高表达，与肿瘤侵袭、转移有一定关系。

Abstract:

Song Hao, Wang Baihe, Shao Xuebao, Cheng Wei, Xiong Jingshu, Wang Xiaopo, Wang Jian, Zeng Xuesi, Xu Xiulian, Sun Jianfang Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China Corresponding authors: Xu Xiulian, Email: xxlqjl@sina.com; Sun Jianfang, Email: fangmin5758@aliyun.com 【Abstract】 Objective To measure the of CC chemokine ligand 18 （CCL18） in cutaneous malignant melanoma （CMM） tissues, and to explore its clinical significance, as well as relationship with vascular endothelial growth factor （VEGF） and Ki67 antigen s. Methods Immunohistochemistry was performed to measure CCL18, VEGF and Ki67 s in 58 paraffin-embedded CMM tissue specimens, as well as CCL18 in 20 paraffin-embedded pigmented nevus specimens, and immunofluorescence assay to confirm the of CCL18 in fresh CMM tissue specimens. Correlations of CCL18 with CMM clinicopathologic features, VEGF and Ki67 s were analyzed. Results CCL18 was detected in 49 （84.48%） of 58 paraffin-embedded CMM specimens, but in none of the 20 paraffin-embedded pigmented nevus specimens, with a significant difference in the positive rate of CCL18 between the CMM group and pigmented nevus group （χ2 = 45.46, P < 0.01）. The of CCL18 in paraffin-embedded CMM tissues was positively correlated with Clark′s level and Breslow thickness of CMM （rs = 0.609, 0.644 respectively, both P < 0.01）, and was significantly different between ulcerated and non-ulcerated CMM （P < 0.05）, as well as between patients with and without lymphatic metastasis （P < 0.05）. However, there were no significant differences in the of CCL18 among patients of different age, gender, or between acral and non-acral CMM （all P > 0.05）. In addition, the of CCL18 in CMM tissues was positively correlated with that of VEGF （rs = 0.727, P < 0.05）, but unrelated to that of Ki67 （P > 0.05）. Immunofluorescence assay showed CCL18 in the cytoplasm of tumor cells in CMM tissues. Conclusion CCL18 is highly expressed in CMM tissues, and may be involved in tumor invasion and metastasis.

宋昊王白鹤邵雪宝程伟熊竞舒王小坡王建曾学思徐秀莲孙建方. CCL18在恶性黑素瘤中的表达及其与血管内皮生长因子、Ki67表达的相关性研究[J]. 中华皮肤科杂志, 2016, 49(10): 688-691.

参考文献 10

［1］	Schutyser E, Richmond A, Van Damme J. Involvement of CC chemokine ligand 18 （CCL18） in normal and pathological processes［J］. J Leukoc Biol, 2005, 78（1）: 14⁃26. DOI: 10.1189/jlb.1204712.
［2］	Su S, Liu Q, Chen J, et al. A positive feedback loop between
	mesenchymal⁃like cancer cells and macrophages is essential to
	breast cancer metastasis［J］. Cancer Cell, 2014, 25（5）: 605⁃620. DOI: 10.1016/j.ccr.2014.03.021.
［3］	Bonecchi R, Locati M, Mantovani A. Chemokines and cancer: a fatal attraction［J］. Cancer Cell, 2011, 19（4）: 434⁃435. DOI: 10.1016/j.ccr.2011.03.017.
［4］	殷芳, 吴飞, 陈佳, 等. 肿瘤相关巨噬细胞对皮肤恶性黑素瘤细胞A375生物学行为的影响［J］. 中华皮肤科杂志, 2014, 47（9）: 619⁃623. DOI: 10.3760/cma.j.issn. 0412⁃4030.2014.09.003.
	Yin F, Wu F, Chen J, et al. Effects of tumor⁃associated macro⁃phages on the biological behavior of A375 human malignant melanoma cells［J］. Chin J Dermatol, 2014, 47（9）: 619⁃623. DOI: 10.3760/cma.j.issn.0412⁃4030.2014. 09.003.
［5］	辛崇美, 李光, 孙建方, 等. CCL18趋化性细胞因子对A375黑素瘤细胞株增殖和侵袭的影响［J］. 中华皮肤科杂志, 2010, 43（12）: 833⁃836.
	Xin CM, Li G, Sun JF, et al. Effects of chemokine CCL18 on the proliferation and invasion of a human melanoma cell line A375 ［J］. Chin J Dermatol, 2010, 43（12）: 833⁃836.
［6］	Gao J, Li ZH, Tang W, et al. Chemokine C⁃C motif ligand 18 correlates with tumor malignancy in breast cancer［J］. Pathol Biol （Paris）, 2015, 63（4⁃5）: 199⁃203. DOI: 10.1016/j.patbio.2015.07.001.
［7］	Wang Q, Tang Y, Yu H, et al. CCL18 from tumor⁃cells promotes epithelial ovarian cancer metastasis via mTOR signaling pathway［J/OL］. Mol Carcinog, 2015［2016⁃1⁃4］. http://onlinelibrary.wiley.com/doi/10.1002/mc.22419/full. ［Publish online ahead of print Oct 12, 2015］. DOI: 10.1002/mc.22419.
［8］	王宝娜, 王翔, 张增海, 等. Ki67在乳腺癌中的表达及临床意义［J］. 中华肿瘤杂志, 2014, 36（4）: 273⁃275.
	Wang B, Wang X, Wang J, et al. Expression of Ki67 and clinicopathological features in breast cancer［J］. Chin J Oncol, 2014, 36（4）: 273⁃275. DOI: 10.3760/cma.j.issn.0253⁃3766.2014. 04.007.
［9］	Felcht M, Thomas M. Angiogenesis in malignant melanoma［J］. J Dtsch Dermatol Ges, 2015, 13（2）: 125⁃136. DOI: 10.1111/ddg. 12580.
［10］	Brychtova S, Bezdekova M, Brychta T, et al. The role of vascular endothelial growth factors and their receptors in malignant melanomas［J］. Neoplasma, 2008, 55（4）: 273⁃279.