半乳糖凝集素-3蛋白和mRNA在眼部静脉血管畸形组织中的表达及意义

The expressions of Galectin-3 protein and mRNA in venous malformation of ocular region and its clinical significance

背景 眼部静脉血管畸形呈终生渐进性发展,并表现出局部侵袭的恶性生物学行为,对局部组织器官造成形态及功能损害.研究表明,半乳糖凝集素-3（Gal-3）与恶性肿瘤的局部侵袭密切相关,研究其在眼部静脉畸形局部侵袭中的作用对治疗的选择具有重要意义.目的 研究Gal-3蛋白和mRNA在眼部静脉畸形组织中的表达及其与临床特征的关联性.方法 收集2009年6月至2014年6月在河南省人民医院血管瘤外科和河南省眼科研究所手术切除的118例眼部静脉畸形病理标本进行检测,采用免疫组织化学染色法及原位杂交方法检测眼部静脉畸形组织中Gal-3蛋白及其mRNA的表达,以20例经病理组织学证实正常的病理标本远端切缘作为对照.将患者分为Gal-3蛋白和mRNA阳性表达组和阴性表达组,比较2个组间患者病变组织中Gal-3表达与病变侵袭深度及病变形状和边界清晰度的关联.结果 常规组织病理学检查表明,眼部静脉血管畸形组织中含有多数中到大管径的血管腔隙,内衬扁平内皮细胞,免疫组织化学染色法及原位杂交方法检测显示Gal-3蛋白及其mRNA均表达于细胞质及细胞核,呈棕褐色染色.眼部静脉畸形组织中Gal-3蛋白阳性表达率为55.93％（66/118）,明显高于远端手术切缘正常组织的15.00％ （3/20）,差异有统计学意义（x2 =11.461,P＜0.05）.眼部静脉畸形组织中Gal-3 mRNA的阳性表达率为59.32％ （70/118）,明显高于远端手术切缘正常组织的20.00％（4/20）,差异有统计学意义（x2=10.633,P＜0.05）.≤12岁与＞12岁患者之间及不同性别间Gal-3蛋白和mRNA的阳性表达率均无统计学意义（年龄x2=0.334、0.128,均P＞0.05;性别：x2 =0.606、1.155,均P＞0.05）;Gal-3蛋白及mRNA阳性表达组累及跟肌等深部组织的病变发生率明显高于Gal-3蛋白及mRNA阴性表达组,差异均有统计学意义（x2=32.688、23.695,均P＜0.05）;Gal-3蛋白及mRNA阴性表达组病变呈球形且边界清楚者分别占96.15％和97.92％,Gal-3蛋白及其mRNA阳性表达组呈筛孔状且边界不清楚的病变率明显高于Gal-3蛋白及其mRNA阴性表达组,差异均有统计学意义（x2=28.255、28.186,均P＜0.05）.结论 有深层组织侵袭的眼部静脉畸形组织患者病变组织中Gal-3的阳性表达率升高,Gal-3表达阳性的眼部静脉畸形组织边界不清,提示眼部静脉畸形患者病变的局部侵袭破坏与Gal-3表达上调有关.

Background Venous malformation damages the local tissue severely because of the progressive development and often presents with invasive biological behavior.Galectin-3 （Gal-3） is proved to be closely associated with local invasion of malignant tumor.Studying the role of Gal-3 on tissue invasion in venous malformation of ocular region is of important clinical significance.Objective This study was to explore the role of Gal-3 protein and mRNA expression in venous malformation of ocular region.Methods One hundred and eighteen pathological sections were collected from ocular venous malformation patients who received surgery in Department of Hemangioma Surgery,People＆#39;s Hospital of Henan Province and Henan Eye Institute from June 2009 to June 2014.The specimens were further diagnosed by histopathological examination.Then the expressions of Gal-3 protein and mRNA in venous malformation of ocular region were detected by using immunohistochemistry and in situ hybridization and compared with 20 pieces of distal cutting edge specimens which were evidently normal.The associations of Gal-3 positive expressions with invasion and configuration of lesions were analyzed.Results Pathological examination showed that venous malformations tissues contain many big blood vessels lacuna, lined with fiat endothelial cells.Immunochemistry and in situ hybridization exhibited that Gal-3 protein and mRNA were expressed in the cytoplasm and nuclei.The positive expression rates of Gal-3 protein and mRNA in the venous malformation tissues were 55.93% （66/118） and 59.32% （70/118） , but those in the normal tissue were 15.00% （3/20） and 20.00% （4/20） ,showing significant differences between them （x2 =11.461, 10.633, both at P〈0.05）.No significant differences were seen in the positive expression rates of Gal-3 protein and mRNA between the patients aged ≤ 12 years and 〉12 years or different genders （age： x2 =0.334,0.128;both at P〉0.05.gender：x2 =0.606,1.155;both at P 〉0.05）.The incidence rate of invading ocular deep tissues was significantly higher in the Gal-3-positive groups than that in the Gal-3-negative groups of protein and mRNA （protein ：x2 =32.688, P〈0.05;mRNA ： x2 =23.695, P〈0.05）.In the Gal-3-negative groups,96.15% （Gal-3 protein negative group） and 97.92% （Gal-3 mRNA negative group） lesions showed the spherical shape with clear boundaries.The lesions texture with the fuzzy boundaries and the incidences of vague structure in lesions were significantly higher in the Gal-3-positive groups than that in the Gal-3-negative groups of protein and mRNA （protein ：x2 =28.255, P〈0.05;mRNA ： 28.186, P〈0.05）.Conclusions Gal-3 expression rate is raised in the deep tissue-invaded and texture disorder ocular venous malformation.These results suggest that invasion and damage of ocular venous malformation are associated with the up-regulation of Gal-3.