不同基因突变的醛固酮瘤患者的临床生化及免疫组化特征  

Clinical,biochemical and immunohistological characteristics in patients of aldosterone producing adenoma with different genetic mutations

作　　者：陈亮[1] 宋颖[1] 肖明 何文雯[1] 梅玫[1] 程庆丰[1] 汪志红[1] 李佳渝 杨淑敏[1] 胡金波[1] 李启富[1] 杨溢[1] Chen Liang;Song Ying;Xiao Ming;He Wenwen;Mei Mei;Cheng Qingfeng;Wang Zhihong;Li Jiayu;Yang Shumin;Hu Jinbo;Li Qifu;Yang Yi(Department of Endocrinology,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China;Department of Pathology,College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China;Lipid and Glucose Metabolism Laboratory,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学附属第一医院,内分泌科,400016 [2]重庆医科大学,基础医学院,病理学教研室,400016 [3]重庆医科大学附属第一医院,脂糖代谢实验室,400016

出　　处：《中华内分泌代谢杂志》2021年第1期45-51,共7页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(81670785、81800701、81870567、81800731、81970720)。

摘　　要：目的探讨不同基因突变的醛固酮瘤(APA)患者的临床生化及免疫组化染色特征。方法纳入接受单侧肾上腺切除的APA患者206例,搜集其临床和生化资料。通过Sanger测序对其术后标本行KCNJ5等基因的突变检测,以及对标本进行11β-羟化酶(CYP11B1)和醛固酮合成酶(CYP11B2)染色,并进行H-score定量评分。结果206例APA患者中,166例(80.6%)检出基因突变,其中158例为KCNJ5突变,2例ATP1A1突变,5例ATP2B3突变,1例CTNNB1突变。突变组APA患者的年龄、高血压病程、血钾均显著低于无突变组(P<0.05);其女性患者比例、收缩压、舒张压、醛固酮/肾素比值(ARR)和盐水负荷试验(SIT)后血浆醛固酮水平(PAC)均显著高于无突变组(P<0.05)。亚组分析显示,ATP酶(ATP1A1和ATP2B3)突变APA患者的年龄、高血压病程、收缩压和左心室肥厚患者比例均显著高于KCNJ5突变组(P<0.05);其SIT后PAC和肿瘤直径均显著低于KCNJ5突变组(P<0.05)。在免疫组化水平,不同突变的APA中CYP11B2染色的阳性率无显著差异。H-score分析显示KCNJ5突变APA的CYP11B1的H-score评分显著高于ATP酶突变组[160.0(127.5,193.5)对80.0(27.5,152.3),P=0.020],而CYP11B2的H-score评分显著低于ATP酶突变组[155.0(123.0,190.0)对240.0(140.0,270.0),P<0.01]。结论APA患者的基因突变类型与其临床生化表型和分子病理表型有密切的关系。Objective To investigated the clinical,biochemical,and immunohistological characteristics of patients with aldosterone producing adenoma(APA)and different gene mutations.Methods The clinical and biochemical data of 206 patients with APA who received unilateral adrenalectomy were collected.Sanger sequencing was used to identify the mutation in the hot-point of KCNJ5 and other genes.The tumor samples were stained by 11β-hydroxylase(CYP11B1)and aldosterone synthase(CYP11B2),which was quantified by McCarty′s H-score system.Results The gene mutations were identified in 166 out of 206(80.6%)patients with APA,of which 158 cases were KCNJ5 mutation,2 ATP1A1 mutation,5 ATP2B3 mutation,and 1 CTNNB1 mutation.Age,duration of hypertension,and serum potassium in APA patients with genetic mutant were significantly lower than those without genetic mutation(P<0.05)while the proportion of female,systolic blood pressure,diastolic blood pressure,aldosterone/renin ratio(ARR),and plasma aldosterone concentration(PAC)post saline infusion test(SIT)were significantly higher(P<0.05).Subgroup analysis showed that age,duration of hypertension,systolic blood pressure,and proportion of left ventricular hypertrophy in APA patients with ATP1A1 and ATP2B3 mutations were significantly higher than those with KCNJ5 mutation(P<0.05)while the PAC post SIT and tumor diameter were significantly lower(P<0.05).The positive rates of CYP11B2 in APA with different mutations were not significantly different.The H-score of CYP11B1 was significantly higher[160.0(127.5,193.5)vs 80.0(27.5,152.3),P=0.020]and the H-score of CYP11B2 was significantly lower[155.0(123.0,190.0)vs 240.0(140.0,270.0),P<0.01]in APA with KCNJ5 mutation compared with those with ATPase mutation.Conclusion The types of genetic mutation are closely correlated with the clinical,biochemical,and immunohistological phenotypes in patients with APA.

关 键 词：醛固酮瘤 基因突变 11β-羟化酶 醛固酮合成酶 临床生化特征 

分 类 号：R586.24[医药卫生—内分泌]