星形胶质细胞活化基因-1(AEG-1)在葡萄膜黑色素瘤中的表达及其与临床组织病理学的关系

Expression of astrocyte elevated gene-1 (AEG-1) in uveal melanoma and its relationship with clinical histopathology

目的研究葡萄膜黑色素瘤(uveal melanoma,UM)组织中星形胶质细胞活化基因-1(astrocyte elevated gene-1,AEG-1)的表达及其与临床组织病理学的关系。方法收集北京同仁医院眼科2013年1月至2017年5月,经眼科病理室确诊为UM且临床资料完善的50例患者(50眼)UM石蜡组织标本为实验组,11例(11眼)因外伤行眼球摘除但大部分葡萄膜组织正常的石蜡组织标本为对照组。应用免疫组织化学法检测所有石蜡标本中氉AEG-1的表达,并分析UM临床病理学特征与AEG-1的相关性。结果 AEG-1蛋白染色呈粉红色或者红色,主要定位于UM核周、细胞浆和细胞膜。实验组中,AEG-1阴性表达21眼(42.0%),阳性表达29眼(58.0%);对照组中AEG-1均呈阴性表达,两组AEG-1表达比较差异有显著统计学意义(P=0.000),提示AEG-1在UM中高表达。在实验组中,当UM患眼存在临床组织病理学高危因素时,即存在肿瘤累及睫状体、虹膜新生血管生成、肿瘤基底最大直径>16 mm、肿瘤高度>8 mm、肿瘤细胞为混合细胞型、肿瘤细胞属于上皮样或混合细胞型、肿瘤眼外生长的患者,其AEG-1阳性表达率分别为73.1%、73.9%、95.2%、82.4%、83.3%、74.1%、69.4%,明显高于非高危因素患者,以上各特征组AEG-1表达比较差异均有统计学意义(均为P<0.05)。而患者性别、眼别、年龄、累及视盘与否、继发视网膜脱离与否、上皮样细胞型、侵犯巩膜导管与否组AEG-1表达差异均无统计学意义(均为P>0.05)。结论 AEG-1在UM组织中高表达,且与UM临床组织病理学多种高危因素呈显著相关性,提示AEG-1的高表达有可能成为判断UM患者预后的重要指标之一。

Objective To investigate the relationship between the expression of astrocyte elevated gene-1(AEG-1)and its clinical pathological features in uveal melanoma.Methods Paraffin tissue specimens of 50 patients(50 eyes)with confirmed diagnosis of uveal melanoma(UM)were collected as experimental group,and samples from 11 patients(11 eyes)who underwent ocular excision due to trauma,still with largely intact uveal tissue,were selected as control group in the Department of Ophthalmology of Beijing Tongren Hospital from January 2013 to May 2017.Then the expression of AEG-1 in paraffin-embedded specimens was detected by immunohistochemical methods,and the correlation of AEG-1 expression with the clinical pathological data was analyzed.Results AEG-1 protein staining presented accurate pink or red granules,mainly located in UM nucleus,cytoplasm,cell membrane.In the experimental group,negative expression of AEG-1 was in 21 eyes(42.0%),and positive expression was in 29 eyes(58.0%),while AEG-1 were negatively expressed in the control group,and the difference in the two groups was statistically significant(P=0.000),suggesting that the expression of AEG-1 was upregulated in UM.In the experimental group,AEG-1 positive expression rate in patients with clinical pathological risk factors was significantly higher than that in patients without high risk factors(all P<0.05),and the positive expression rate of AEG-1 in UM with involvement of the ciliary body and iris neovascularization,the maximum diameter of tumor base>16 mm,tumor thickness>8 mm,tumor cell type belonging to mixed cell type and epithelioid/mixed cell type,and extra ocular tumor growth was 73.1%,73.9%,95.2%,82.4%,83.3%,74.1%and 69.4%,respectively.However,there was no significant difference in AEG-1 expression among general clinical data including gender,eyes,age,optic disc involvement,secondary retinal detachment,epithelioid cell type and scleral duct invasion(all P>0.05).Conclusion AEG-1 is overexpressed in UM and has a significant correlation with multiple clinical risk factors,suggesting that high expression of AEG-1 may be one of the important prognostic indicators for UM.