皮肤恶性黑素瘤肿瘤相关巨噬细胞与上皮间质化指标相关性的研究

Correlation analysis between tumor-associated macrophages and epithelial-mesenchymal transition in cutaneous malignant melanoma

目的 探讨皮肤恶性黑素瘤标本肿瘤相关巨噬细胞（TAM）浸润情况与肿瘤临床病理特征及上皮间质化指标之间的关系.方法 收集54例皮肤黑素瘤及15例良性色素痣石蜡标本,用免疫组化法对TAM标记CD163及上皮间质化指标上皮型钙黏蛋白、神经型钙黏蛋白及波形蛋白在组织中的表达进行检测.采用SPSS 17.0统计软件进行数据分析,计量资料（x）±s表示,采用t检验、单因素方差分析、多因素线性回归进行数据分析.结果 恶性黑素瘤标本中检测到CD163阳性的TAM,在色素痣标本中未发现明显的CD163阳性细胞.在原位黑素瘤中,TAM计数为16.97±8.74,在侵袭性黑素瘤中,TAM计数为35.08±13.78,差异有统计学意义（P＜0.05）.在有淋巴结转移的TAM计数为56.00±3.07,在无淋巴结转移的TAM计数为28.70±18.52,差异有统计学意义（P＜0.05）.TAM计数在Clark分级中差异有统计学意义（P＜0.05）,且在Ⅰ～Ⅳ级TAM计数随Clark级别增高而增加,Ⅳ级与Ⅴ级之间的TAM计数,差异无统计学意义（P＞0.05）.TAM计数在不同性别、不同年龄、肢端/非肢端、是否溃疡之间比较,差异无统计学意义（P≥0.05）.多因素线性回归结果显示,皮肤恶性黑素瘤组织中,TAM计数与Clark分级、溃疡、肿瘤进展、神经型钙黏蛋白及波形蛋白5个因素相关.结论 皮肤恶性黑素瘤中TAM可能通过促进上皮间质化使肿瘤发展,从而增加肿瘤的恶性程度.

Objective To investigate the relationship of tumor-associated macrophage （TAM） infiltration in lesions with clinicopathologic features of cutaneous malignant melanoma （CMM） and epithelialmesenchymal transition （EMT）-related indicators.Methods Fifty-four CMM and 15 benign melanocytic nevus paraffin-embedded tissue samples were collected.An immunohistochemical study was performed to determine the expression pattern and intensity of the TAM marker CD163 as well as EMT indicators epithelial cadherin （E-cadherin）,neurologic cadherin （N-cadherin） and vimentin in these tissue samples.Count data were expressed as mean ± standard deviation.Statistical analysis was carried out using t test,one-way analysis of variance （ANOVA） and multivariate linear regression analysis with the software SPSS 17.0.Results CD163-positive TAMs were detected in CMM samples,but not in benign melanocytic nevus samples.The mean TAM count per high power field in tissue samples was significantly different between invasive and in situ CMM （35.08 ± 13.78 vs.16.97 ± 8.74,P 〈 0.05）,and between melanoma with lymph node metastasis and that without （56.00 ± 3.07 vs.28.70 ± 18.52,P 〈 0.05）,and among melanoma with different Clark levels （P 〈 0.05）.Additionally,the mean TAM count increased with the increase in Clark level from Ⅰ to Ⅳ,but was insignificantly different between Clark level Ⅳ and Ⅴ （P 〉 0.05）.No significant difference was observed in TAM count between patients of different gender or age groups,between acral and non-acral melanoma,or between ulcerated and non-ulcerated melanoma （all P ≥ 0.05）.Multivariate linear regression analysis showed that TAM count in CMM was associated with five factors：Clark level,ulceration,tumor progression,N-cadherin and vimentin.Conclusion TAMs may accelerate tumor progression and increase tumor malignancy by promoting EMT in CMM.