卡波西样血管内皮瘤伴卡梅现象患儿GRα、GRβ的表达与激素敏感性的关系

The relationship between the expression of GRα、GRβ and hormone sensitivity in KHE childrenwith KMP

目的探讨卡波西样血管内皮瘤（KHE）伴卡梅现象（KMP）患儿糖皮质激素受体（GRα、GRβ）的表达与激素敏感性的关系。方法收集自2013年5月年至2016年5月在河南省人民医院治疗的KHE伴KMP的患儿，符合入选标准者25例，男9例，女16例，平均年龄为（2.4±1.5）个月。对患儿进行为期1周的糖皮质激素治疗，根据疗效评判标准分为敏感组（10例）和抵抗组（15例）。激素治疗1周，待条件具备后，采用手术切除瘤体。以外科手术切除的15例（脂肪瘤）多余的健康组织作为对照组。对手术切除组织进行免疫组化SP法检测。根据GRα和GRβ的表达强度和阳性细胞比例分别建立数据库，成组样本应用Wilcoxon秩和检验，多样本应用Kruskal-Wallis法检验，比较分析敏感组、抵抗组、对照组GRα、GRβ阳性表达的数量、强度和分布特点，以P〈0.05为差异有统计学意义。结果①对照组、敏感组、抵抗组GRα的表达强度分别为4.20±1.01、4.10±0.99、3.53±0.52，3组比较差异无统计学意义（P=0.632）。敏感组GRα阳性细胞数量为46.20±2.57，高于抵抗组的40.93±5.18（P=0.032）。②GRβ的表达强度在抵抗组（5.40±0.51）中显著高于敏感组（2.60±0.52）和对照组（2.87±0.64）（P=0.000、0.002）；GRβ阳性细胞数量在敏感组（29.70±2.50）、对照组（36.07±3.47）、抵抗组（47.27±5.59）中呈逐渐上升趋势，且差异有统计学意义（P=0.000）。③GRα/GRβ表达强度的比值在抵抗组中显著低于敏感组、对照组（P=0.003、0.003）；GRα/GRβ阳性细胞数量的比值在敏感组、对照组、抵抗组中呈逐渐下降趋势，且差异有统计学意义（P=0.000）。结论KHE伴KMP患儿瘤体组织中，GRβ表达的增高对GRα起负性调节作用，导致两者表达比例的平衡失调，可能是GC抵抗的重要原因。

To investigate the relationship between glucocorticoid receptor （GRα、GRβ ） expression and hormone sensitivity in kaposiform hemangioendothelioma （KHE） patients complicated by Kasabach- Merritt phenomenon （KMP）. Methods In this study, 25 cases of KHE with KMP （mean age 2.4 ± 1.5 months） , including 9 males and 16 females at Henan Provincial People＇s Hospital between May 2013 and May 2016 were included. All patients underwent surgical resection after being treated with hormone for one week, and were divided into sensitive group （10 cases） and resistance group （15 cases） according to the efficacy evaluation criteria. Normal tissues collected from 15 patients received surgical excision of lipoma was performed as a control group. Immunohistrochemical SP method was adopted in detecting GRα and GRβ expression in all groups. The expression intensity and positive rate were analyzed. Statistical significance was determined using the Wileoxon rank sum test for the group samples and the Kruskal-Wallis test for multiple samples. Values of P 〈 0.05 were considered statistically significant. Results ①There was no significant difference among the control group, the resistance group and the sensitive group in expression intensity of GRα （ control group 4.20± 1.01 ,resistance group 4.10 - 0.99, sensitive group 3.53 ± 0.52, P = 0. 632）. The number of GRα positive cells in the sensitive group（46.20 ± 2.57 ）was higher than that in the resistance group （40.93 ± 5. 18, P = 0. 032 ）. ②The expression intensity of GRβ in the resistance group（5.40 ±0.51 ） was significantly higher than that in the sensitive group （ 2.60± 0.52 ） and the control group （2.87 ±0. 64, P = 0. 000,0. 002） ; there was significant difference among the sensitive group （ 29.70 ± 2.50 ） , the control group （ 36.07 ± 3.47 ） and the resistance group （47.27 ± 5.59 ） in the number of GRβ positive cells （P = 0. 000）. ③The ratio of GRα/GRβ expression intensity was significantly lower in the resistance group than in the sensitive group and the control group ; The ratio of GRα/GRβ positive cells was gradually decreased in the sensitive group, control group and resistance group, and the difference was statistically significant （P = 0. 000）. Conclusions In the tumor tissue of KHE children with KMP, the increase of GRβ expression negatively regulats GRα, leading to imbalance of the expression ratio of the two, which may be an important cause for GC resistance.