少突胶质细胞瘤染色体1p/19 q杂合性缺失与p53蛋白表达的相关性研究

目的 探讨少突胶质细胞瘤染色体1p/19q杂合性缺失及p53蛋白的表达情况,与星形细胞起源的肿瘤进行比较研究并探讨其意义.方法 选择2004-2005年间,经病理组织学诊断为不同类型和级别的胶质瘤合计191例,包括:WHOⅡ级少突胶质细胞瘤116例,其中30例为新鲜组织;间变性少突胶质细胞瘤45例和不同级别星形细胞起源的肿瘤石蜡组织30例;采用PCR-微卫星技术检测染色体1p/19q杂合性缺失情况;采用免疫组织化学方法 对184例胶质瘤石蜡切片p53蛋白表达情况进行半定量分析.结果 86例WHO Ⅱ级少突胶质细胞瘤石蜡标本染色体1p缺失率为69.8%(60/86)、19q缺失率为64.0%(55/86)、1p/19q联合缺失率为57.0%(49/86);45例间变性少突胶质细胞瘤中,1p缺失率为71.1%(32/45)、19q缺失率为60.0%(27/45)、1p/19q联合缺失率为55.6%(25/45);两种级别间差异无统计学意义(P>0.05).30例WHO Ⅱ级少突胶质细胞瘤新鲜标本染色体1p缺失率为70.0%(21/30)、19q缺失率为63.3%(19/30)、1p/19q联合缺失率为60.0%(18/30),与石蜡标本的缺失率比较差异无统计学意义(P>0.05).30例星形细胞起源的肿瘤染色体对应三种缺失率分别为23.3%(7/30)、33.3%(10/30)及20.0%(6/30),与少突胶质细胞瘤差异有统计学意义(P<0.05).86例WHO Ⅱ级少突胶质细胞瘤中,仅7例有p53蛋白阳性表达(占8.1%);45例间变性少突胶质细胞瘤中,有14例呈阳性表达(31.1%),两者差异有统计学意义(P=0.007).少突胶质细胞瘤p53蛋白阳性表达明显低于星形细胞起源的肿瘤(P=0.001).在间变性少突胶质细胞瘤中,染色体1p/19q杂合性缺失与p53蛋白阳性表达呈负相关(P<0.05).结论 石蜡和新鲜组织均可用于染色体1p/19q杂合性缺失的检测.在间变性少突胶质细胞瘤中,染色体1p/19q杂合性缺失与p53蛋白阳性表达呈负相关.检测少突胶质细胞瘤染色体1p/19q杂合性缺失和p53蛋白表达,对提高病理诊断的精确性、指导治疗及预后判断具有重要意义.

Loss of heterozygosity of chromosome 1p/19q and p53 protein expression in oligodendroglioma

Objective To study the status of loss of heterozygosity ( LOH) of chromosome lp/19q and p53 protein expression in oligodendroglioma,as compared to astrocytoma.Methods One hundred and ninety-one cases of glioma of different histologic types and grades,including 116 cases of low-grade of oligodendroglioma ( 86 paraffin-embedded and 30 fresh tissues) ,45 cases of anaplastic oligodendroglioma (all paraffin-embedded tissues) and 30 cases of astrocytoma of various grades ( all paraffin-embedded tissues),were enrolled into the study.The LOH of chromosome lp/19q was investigated by polymerase chain reaction ( PCR) -based microsatellite analysis.The p53 protein expression was demonstrated by immunohistochemical staining.Results The rates of lp loss, 19q loss and lp/19q loss were 69.8% ,64%,and 57.0% respectively in the 86 paraffin-embedded low-grade oligodendroglioma samples,as compared to 71.1%,60.0% and 55.6% respectively in the 45 paraffin-embedded anaplastic oligodendroglioma samples.There was no difference of LOH of lp/19q between low-grade oligodendroglioma and anaplastic oligodendroglioma (P > 0.05).In the 30 cases of low-grade oligodendroglioma with fresh tissues available,the rates of lp loss,19q loss and lp/19q loss were 70.0%,63.3% and 60.0% respectively.The LOH of lp/19q between paraffin-embedded and fresh samples was not statistically significant (P >0.05).In the 30 cases of astrocytoma,the rates of lp loss,19q loss and lp/19q loss were 23.3%,33.3% and 20.0% respectively,which were significantly less than those in oligodendroglioma (P < 0.05).The expression of p53 protein was significantly lower in low-grade oligodendroglioma (8.1 % ) than in anaplastic oligodendroglioma (31.1%,P = 0.007).The expression of p53 protein in oligodendroglioma was also lower than in astrocytoma ( P = 0.001 ).Furthermore,p53 protein expression negatively correlated with lp/19q loss in anaplastic oligodendroglioma (P <0.05).Conclusions Both paraffin-embedded and fresh tissues are suitable for analysis of LOH of chromosome lp/19q.Oligodendroglioma demonstrates a higher frequency of LOH of chromosome lp/19q and lower expression of p53 protein than astrocytoma.The LOH of chromosome lp/19q negatively correlates with the expression of p53 protein.These parameters have both diagnostic and prognostic values.