Huang Lei, Jiang Tao, Yuan Fang, Li Gui-lin, Xu Li-xin, Cui Yun
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Zhonghua Zhong Liu Za Zhi. 2011 Oct;33(10):752-8.
To study the correlation of loss of heterozygosity (LOH) on chromosome 1p and 19q with the expression of MGMT, p53 and Ki-67 proteins in gliomas.
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 high-performance liquid chromatography (DHPLC) for 1p 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.
In the oligodendrogliomas, the positive rate of 1p LOH was 59.8%, significantly higher than 33.9% in astrocytomas (P = 0.002), and 1p 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%). 1p 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.
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.
研究1p和19号染色体杂合性缺失（LOH）与胶质瘤中MGMT、p53和Ki-67蛋白表达的相关性。
本研究纳入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）。采用聚合酶链反应-变性高效液相色谱法（PCR-DHPLC）对其组织和血液样本进行回顾性分析，以检测1p和19q状态，并采用免疫组织化学法检测MGMT、p53和Ki-67的表达模式。通过卡方检验和t检验分析它们之间的相关性以及与临床病理特征的相关性。
在少突胶质细胞瘤中，1p LOH的阳性率为59.8%，显著高于星形细胞瘤中的33.9%（P = 0.002）；1p和19q LOH为42.5%，显著高于星形细胞瘤中的16.9%（P = 0.001）。与1p和19q LOH相结合，少突胶质细胞瘤中低MGMT表达（65.5%）和高Ki-67表达（54%）更为常见，而高p53表达在星形细胞瘤和混合性肿瘤中更为常见（75.2%）。在II级少突胶质细胞瘤中，1p LOH（72.5%）和低MGMT（87.5%）表达更为常见，而在III级少突胶质细胞瘤中，p53（83.0%）和Ki-67（76.6%）高表达更为常见。此外，III级星形细胞瘤中高Ki-67表达更为常见。非颞叶少突胶质细胞瘤中1p和19q LOH（55.6%）比颞叶少突胶质细胞瘤中（22.2%，P = 0.002）更为常见。发现1p LOH与19q LOH、MGMT与p53蛋白表达以及MGMT与Ki-67蛋白表达之间存在非随机关联（均P < 0.05），而1p和19q LOH与p53表达之间以及1p LOH与Ki-67表达之间存在相互排斥。
所研究的分子标志物与胶质瘤的临床病理特征之间存在显著的相互关系，这支持了分子标志物在指导胶质瘤的诊断评估和临床管理中具有重要作用。
