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

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

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（χ^2=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。

Objective To measure the expression 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 expressions. Methods Immunohistochemistry was performed to measure CCL18, VEGF and Ki67 expressions in 58 paraffin-embedded CMM tissue specimens, as well as CCL18 expression in 20 paraffin-embedded pigmented nevus specimens, and immunofluorescence assay to confirm the expression of CCL18 in fresh CMM tissue specimens. Correlations of CCL18 expression with CMM clinicopathologic features, VEGF and Ki67 expressions 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（χ^2=45.46, P〈0.01）. The expression 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 expression of CCL18 among patients of different age, gender, or between acral and non-acral CMM（all P〉0.05）. In addition, the expression 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 expression 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.