胶质瘤染色体1p和19q杂合性缺失与O6-甲基鸟嘌呤DNA甲基转移酶p53和Ki-67蛋白表达的关系

目的 探讨胶质瘤染色体1p和19q杂合性缺失(LOH)与O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)、p53和Ki-67蛋白表达的关系.方法 采集146例胶质瘤(45例少突胶质细胞瘤、42例少突星形细胞瘤和59例星形细胞瘤)的肿瘤组织和血液标本,采用聚合酶链反应结合变性高效液相色谱技术检测染色体1p和19q LOH,免疫组化法检测肿瘤组织中MGMT、p53和Ki-67蛋白的表达,并进一步分析其与胶质瘤临床病理特征的关系.结果 少突胶质细胞肿瘤和星形细胞瘤中,1p LOH的发生率分别为59.8％和33.9％,差异有统计学意义(P=0.002);1p和19q LOH的发生率分别为42.5％和16.9％,差异有统计学意义(P=0.001).MGMT低表达和Ki-67高表达多发生于少突胶质细胞肿瘤中,发生率分别为65.5％和54.0％,而p53高表达多发生于星形细胞瘤和少突星形细胞瘤中,发生率为75.2％.在87例少突胶质细胞肿瘤中,1p LOH和MGMT蛋白低表达多发生于Ⅱ级少突胶质细胞肿瘤中,发生率分别为72.5％和87.5％,而p53和Ki-67蛋白高表达多发生于Ⅲ级少突胶质细胞肿瘤中,发生率分别为83.0％和76.6％.1p和19q LOH在非颞叶和颞叶肿瘤的发生率分别为55.6％和21.2％(P=0.002).1p LOH与19q LOH、MGMT蛋白表达与p53蛋白表达、MGMT蛋白表达与Ki-67蛋白表达、1p和19q LOH与p53蛋白表达、1p LOH与Ki-67蛋白表达均有关(均P＜0.05).结论 1p和19q LOH及MGMT、p53和Ki-67的蛋白表达与胶质瘤的临床病理学特征有关,检测其LOH状态和表达水平对胶质瘤的诊断和治疗具有指导作用.

Correlation between loss of heterozygosity on chromosome 1p and 19q and expression of MGMT, p53 and Ki-67 proteins in gliomas

Objective To study the correlation of loss of heterozygosity(LOH)on chromosome 1 p and 19q with the expression of MGMT,p53 and Ki-67 proteins in gliomas.Methods One hundred and forty six cases of gliomas(45 oligodendrogliomas,42 oligodendroastrocytomas,and 59 astrocytomas)were included in this study.Their tissue and blood samples were retrospectively analyzed by PCR-denaturing highperformance liquid chromatography(DHPLC)for 1 p and 19q status and by immunohistochemistry for MGMT,p53 and Ki-67 expression patterns.The correlation among them and with clinicopathological characteristics were analyzed by chi-square test and t-test.Results In the oligodendrogliomas,the positive rate of 1 p LOH was 59.8％,significantly higher than 33.9％ in astrocytomas(P=0.002),and 1 p and 19q LOH was 42.5％,significantly higher than 16.9％ in astrocytomas(P=0.001).Combined with LOH on 1p and 19q,low MGMT expression(65.5％),and high Ki-67 expression(54％)were more frequent in oligodendrogliomas,whereas high p53 expression was more frequent in astrocytomas and mixed tumors(75.2％).1 p LOH(72.5％)and low MGMT(87.5％)expressions were more frequent in grade Ⅱ oligodendrogliomas,whereas high expressions of p53(83.0％)and Ki-67(76.6％)were more frequent in grade Ⅲ oligodendrogliomas.In addition,high Ki-67 expression was more frequent in grade Ⅲ astrocytomas.LOH on 1p and 19q LOH was more frequent in nontemporal oligodendrogliomas(55.6％)than that in temporal ones(22.2％,P=0.002).Non-random associations were found between LOH 1p and 19q LOH,MGMT and p53 protein expressions,and MGMT and Ki-67 protein expressions(all P ＜ 0.05),whereas mutual exclusions were found between LOH on 1p and 19q and p53 expression,and LOH 1p and Ki-67 expression.Conclusions There is a significant interrelationship of the investigated molecular markers and clinicopathological features of gliomas,which support a promising role of molecular markers in guiding diagnostic assessment and clinical management of gliomas.