葡萄膜黑色素瘤中淋巴管生成与组织病理学高危因素关系的研究

Relationship between lymphangiogenesis and the histopathological risk factors of uveal melanoma

目的研究葡萄膜黑色素瘤(UM)组织中肿瘤相关淋巴管生成与肿瘤组织病理学高危因素的关系。设计实验研究。研究对象北京同仁医院眼科病理室2009-2014年55例(55眼)UM眼球石蜡组织标本。方法采用淋巴管内皮特异性标记物LYVE-1和D2-40,通过免疫组织化学Elivision法检测UM组织中淋巴管生成情况,结合患者临床组织病理学资料进行统计学分析;统计肿瘤的微淋巴管密度(lymphatic microvessel density,LMD),结合CD-34检测肿瘤微血管密度(microvessel density,MVD)的结果分析两者的相关性。主要指标UM组织的淋巴管阳性率、LMD、MVD。结果 55例UM组织标本中36例(65.5%)观察到淋巴管。肿瘤累及睫状体者淋巴管阳性率(95.0%)明显高于未累及者(48.6%),发生球外蔓延者淋巴管阳性率(93.3%)明显高于未发生者(55.0%),肿瘤最大基底直径>16 mm者淋巴管阳性率(82.4%)明显高于≤16 mm者(38.1%),上皮样细胞类型者淋巴管阳性率(88.0%)明显高于非上皮样细胞类型者(46.7%)(P均<0.05)。患者年龄(P=0.187)、性别(P=0.452)、眼别(P=0.663)、是否有虹膜新生血管(P=0.395)、是否继发视网膜脱离(P=0.641)、视盘是否受累(P=0.121)、是否浸润巩膜(P=0.284)及术前是否放疗(P=0.483)与UM组织中的淋巴管阳性率均无统计学相关。LMD与MVD成正相关(r=0.917,P<0.001)。结论 2/3的葡萄膜黑色素瘤中存在肿瘤相关淋巴管,其在UM的侵袭转移中可能起到一定的作用。免疫组织化学法检测淋巴管生成是判断UM患者预后的重要指标之一。

Objective To research the relationship between the existence of tumor associated lymphangiogenesis in uveal melanoma（UM） tissues with the histopathological risk factors of UM. Design Experimental study. Participants 55 paraffin embedded eyeball tissues of 55 UM patients with perfect archived clinical data in Beijing Tongren Hospital from 2009 to 2014. Methods The specific lymphatic endothelial markers： LYVE-1 and D2-40, and Elivision immunohistochemical staining method, were used to detect the lymphatic tissue and analyze its relationship with patients＇ clinical pathological data in 55 UM cases. The tumor＇s lymphatic microvessel density（LMD） and microvessel density（MVD） using CD-34 antibody were analyzed. Main Outcome Measures Lymphatic positive rate of different UM tissues, LMD, MVD. Results In 36 cases（65.5%） of the 55 UM tissues the lymphatic vessels were observed. The lymphatic positive rate of tumor involving the ciliary body（95.0%） was significantly higher than that noninvolving（48.6%）, and of tumor spreading outside the eyeball（93.3%） higher than inside（55.0%）, and of tumor with bigger largest tumor basal diameter（16 mm）（82.4%） than the smaller（ ≤ 16 mm）（38.1%）, and of with epithelioid cell type（88.0%） higher than non-epithelioid cell type（46.7%）. The difference all was statistically significant（P0.05）. And the difference of the lymphatic positive rate of UM tissues was not statistically significant between different age（P=0.187）, different gender（P=0.452）, different eye（P=0.663）, whether with iris neovascularization（P=0.935）, with the secondary retinal detachment（P=0.641）, with disc involvement（P=0.121）, with invasion into the sclera（P=0.284）, and whether receiving preoperative radiotherapy（P=0.483）. The lymphatic microvessel density was positive correlation with microvessel density of UM（r=0.917, P〈0.001）. Conclusion Tumor associated lymphangiogenesis is in 2/3 cases of UM, which may play a role in the invasion and metastasis of UM. To detect the lymphangiogenesis of UM with immunohistochemistry staining method may become one of the important index to predict the prognosis.