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中国临床研究英文版:2017,30(9):1169-1173
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脑胶质瘤中ADAM17、EGFR和Ki-67的表达及其与脑胶质瘤恶性程度的关系
(1.承德医学院附属医院神经科,河北 承德 067000;2.秦皇岛市青龙满族自治县医院,河北 秦皇岛 066599;3.承德市第六医院,河北 承德 067200)
Expressions of ADAM17, EGFR and Ki-67 in brain glioma tissues and relationship between their expressions and malignant degree of brain glioma
摘要
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Received:April 06, 2017   Published Online:March 23, 2018
中文摘要: 目的:探讨不同恶性程度脑胶质瘤组织中解聚素-金属蛋白酶17(ADAM17)、表皮生长因子受体(EGFR)和增殖细胞核抗原(Ki-67)的表达及其与肿瘤分级的关系。方法:收集2014年1月至12月神经外科手术切除的人脑胶质瘤新鲜标本40例(脑胶质瘤组f),根据其恶性程度分为低度恶性组f(n=20)和高度恶性组f(n=20),设同期颅脑外伤手术减压的脑组织新鲜标本为对照组f(n=20);免疫印迹法检测新鲜标本ADAM17和EGFR的表达。另收集2010年1月至2013年1月病理科人脑胶质瘤蜡块标本60例(脑胶质瘤组p),分为低度恶性组p(n=23)和高度恶性组p(n=37),设同期颅脑外伤手术减压的脑组织蜡块标本为对照组p(n=9);免疫组化SABC法检测蜡块标本ADAM17、EGFR和Ki 67的表达。分别对不同标本的脑胶质瘤不同恶性程度组织和正常对照组织中ADAM17、EGFR和Ki-67表达情况进行比较。检验水准取α=0.05,采用R×C表χ2检验分割法时,检验水准校正为α′=0.017。结果:新鲜标本的免疫印迹法结果:对照组ADAM17表达极低,EGFR未见表达,ADAM17和EGFR蛋白表达在低度恶性组f(0.32±0.05,0.46±0.07)及高度恶性组f(0.80±0.14,1.16±0.15)均明显增加,且高度恶性组f明显高于低度恶性组f(P均<0.01)。蜡块标本的免疫组化SABC法结果:(1)对照组p ADAM17蛋白以弱阳性表达为主,脑胶质瘤组p ADAM17以阳性和强阳性表达为主;ADAM17蛋白阳性表达率脑胶质瘤组p明显高于对照组p(80.0% vs 22.2%,P<0.01),高度恶性组p明显高于低度恶性组p(94.6% vs 56.5%,P<0.017)。(2)EGFR蛋白在对照组脑组织中无表达,脑胶质瘤中以阳性和强阳性表达为主。EGFR阳性表达率脑胶质瘤组p明显高于对照组p(60.0% vs 0,P<0.01),高度恶性组p明显高于低度恶性组p(73.0% vs 39.1%,P<0.017)。(3)9例对照组Ki-67均为阴性表达;Ki-67阳性表达率脑胶质瘤组p明显高于对照组p(63.3% vs 0,P<0.01),高度恶性组p明显高于低度恶性组p(86.5% vs 26.1%,P<0.017) 。结论:ADAM17、EGFR和Ki-67在脑胶质瘤中表达增加,且随着恶性程度的增高表达水平明显增高,高表达的ADAM17和EGFR与脑胶质瘤细胞增殖密切相关。
Abstract:Objective To investigate the expressions of a disintegrin and metalloprotease domain 17 (ADAM17), epidermal growth factor receptor(EGFR)and proliferating cell nuclear antigen (Ki-67)in brain glioma tissues of different malignant degree. Methods The fresh specimens of human brain glioma (n=40, brain glioma F group) were collected from January to December 2014 and divided into low malignancy group (n=20) and highly malignant group (n=20) according to malignant degree. The fresh brain tissue specimen of surgical decompression for traumatic brain injury were selected as control group (n=20)at the same time. Western blot method was used to detect the expressions of ADAM17 and EGFR in the fresh specimens. On the other hand, paraffin block tissues (n=60, brain glioma group P) of brain glioma were collected from January 2010 to January 2013 and divided into low malignancy group(n=23)and highly malignant group (n=37) according to malignant degree, and the paraffin block tissues of surgical decompression for traumatic brain injury were served as control group(n=9)at the same time. Immunohistochemical SABC methodwas used to detect the expressions of ADAM17, EGFR and Ki-67 proteins, which in different specimens and different malignant degree tissues were compared with those in control group. Statistical test level was α=0.05, and it was corrected as α′=0.017 when using R×C table Chi-square test segmentation method. Results Western blot method for fresh specimens showed that(1) the expression of ADAM17 was very low, and no expression of EGFR was found in control group. (2) the expressions of ADAM17 and EGFR in low malignancy group (0.32±0.05,0.46±0.07)and highly malignant group (0.80±0.14,1.16±0.15)increased significantly, and they in highly malignant group were significantly higher than those in low malignant group (all P<0.01). Immunohistochemical SABC method for paraffin block specimens showed that (1)the expression of ADAM17 protein mainly was weakly positive in control group and mainly was positive and strongly positive in brain glioma group; positive expression rate of ADAM17 protein in brain glioma group was significantly higher than that in control group (80.0% vs 22. 2%, P<0.01)and significantly increased in highly malignant group compared with low malignant group (94. 6%vs 56. 5%, P<0.017). (2)EGFR protein was not expressed in the brain tissue of control group and mainly was positive and strongly positive expressed in brain glioma group; the positive expression rate ofEGFR protein in brain glioma group was significantly higher than that in control group (70.0% vs 0, P<0.01)and significantly increased in highly malignant group compared with low malignant group (73. 0% vs 39. 1%, P<0.017). (3)the expression of Ki-67 protein was all negative in 9 cases of control group, and the positive rate of Ki-67 protein in brain glioma group was significantly higher than that in control group(63. 3% vs 0, P<0.01)and significantly increased in highly malignant group compared with low malignant group (86. 5% vs 26. 1%,P<0.017). Conclusions The expressions of ADAM17, EGFR and Ki-67 increase in brain glioma tissues, and the levels of expression obviously increase with the increase of malignant degree. High expressions of ADAM17 and EGFR are closely related to the proliferation of brain glioma cells.
文章编号:     中图分类号:R739.41    文献标志码:A
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