IDH突变型低级别星形细胞瘤p16蛋白表达与CDKN2A基因缺失状况的相关性  

Association between the expression of p16 protein and the status of CDKN2A gene deletion in low-grade astrocytomas with IDH mutant

作　　者：王春 李昂[1] 郑爱萍[1] 陈嘉康 黄楚强 尹为华[1] 李剑[1] WANG Chun;LI Ang;ZHENG Aiping;CHEN Jiakang;HUANG Chuqiang;YIN Weihua;LI Jian(Department of Pathology,Peking University Shenzhen Hospital,Guangdong Shenzhen 518036,China)

机构地区：[1]北京大学深圳医院病理科,广东深圳518036

出　　处：《现代肿瘤医学》2023年第15期2829-2833,共5页Journal of Modern Oncology

基　　金：广东省深圳市科创委自然科学基金资助(编号:JCYJ20220531094017039)。

摘　　要：目的:以异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)突变型星形细胞瘤为研究对象,探讨利用p16蛋白免疫标记替代CDKN2A基因纯合性缺失检测的可行性。方法:收集我院既往组织学诊断为低级别星形细胞瘤(WHO 2级)且伴有IDH突变的胶质瘤42例,通过免疫组化方法检测肿瘤组织中p16蛋白表达,分别依据其胞核或胞浆阳性表达率将肿瘤分为阴性(阳性率0%)、低表达(0%<阳性率≤10%)、中表达(10%<阳性率≤25%)、高表达(25%<阳性率≤50%)及过表达(阳性率>50%)5个组别;利用FISH方法检测肿瘤CDKN2A基因纯合性缺失与杂合性缺失状况;采用Fisher精确检验评价p16蛋白表达水平与CDKN2A基因缺失间的相关性。结果:胞核p16蛋白表达水平与CDKN2A基因纯合性缺失间存在显著相关(P<0.001)。阴性组(4/4,100%)均检测到CDKN2A纯合性缺失,中、高及过表达组(22/22,100%)均未检测到CDKN2A纯合性缺失。低表达组与CDKN2A纯合性缺失间缺乏明确对应关系,其中3例(3/16,18.75%)检出纯合性缺失,13例(13/16,81.25%)未检出纯合性缺失。胞核p16蛋白表达水平与CDKN2A杂合性缺失无相关(P=0.228)。胞质p16蛋白表达水平与CDKN2A纯合性(P=0.086)或杂合性(P=0.884)缺失均无相关。结论:IDH突变且组织学呈低级别的星形细胞瘤中,胞核p16蛋白阴性(阳性率0%)或中等及以上表达(阳性率>10%)分别提示存在或不存在CDKN2A纯合性缺失。在上述区间p16蛋白与CDKN2A纯合性缺失间存在良好匹配关系,可用于协助病理诊断与分级。胞核p16蛋白低表达(0%<表达率≤10%)则不能预测CDKN2A纯合性缺失状态,此时仍需进行CDKN2A基因层面检测。Objective:To investigate the feasibility of using p16 protein immunostaining as an alternative to replace the homozygous deletion test of cyclin dependent kinase inhibitor 2A(CDKN2A)gene in IDH mutant astrocytomas.Methods:Forty-two cases of glioma with a histological diagnosis of low-grade astrocytoma(WHO grade 2)and concurrently carrying with IDH mutation were retrieved from our hospital.The expression of p16 protein was detected by immunohistochemistry.Based on the expression rate of p16 protein in the nucleus or cytoplasm respectively,the tumors were classified into five groups:Negative(0%positive rate),low expression(0%<positive rate≤10%),moderate expression(10%<positive rate≤25%),high expression(25%<positive rate≤50%),and overexpression(positive rate>50%).Fluorescence in situ hybridization(FISH)was performed to evaluate the homozygous deletion(HmD)and heterozygous deletion(HtD)of CDKN2A gene.Fisher's exact test was employed to evaluate the correlation between p16 protein expression and the deletion status of CDKN2A gene.Results:The expression level of p16 protein in the nucleus was significantly correlated with CDKN2A HmD(P<0.001).The cases in the negative expression group(4/4,100%)consistently showed CDKN2A HmD,while no cases in the moderate,high,and overexpression groups(22/22,100%)demonstrated HmD.However,no constant relationship was observed in p16 low expression group,as 3 cases(3/16,18.75%)detected HmD while 13 cases(13/16,81.25%)did not.On the other hand,p16 protein expression in the nucleus did not correlate with CDKN2A HtD(P=0.228).In addition,p16 protein expression in the cytoplasm did not correlate with either CDKN2A HmD(P=0.086)or HtD(P=0.884).Conclusion:As far as the histologically low-grade astrocytoma with IDH mutant was concerned,the negative expression(0%positive rate)or moderate and above expression(positive rate>10%)of p16 protein in the nucleus suggested the presence or absence of CDKN2A HmD,respectively.In the above expression range,p16 protein exhibited well-matched relationships

关 键 词：星形细胞瘤 IDH突变 P16蛋白 CDKN2A基因 

分 类 号：R739.4[医药卫生—肿瘤]