首都医科大学三博脑科医院病理科 姚坤 段泽君 边宇 马忠 齐雪岭

【摘要】目的 观察少突胶质细胞起源肿瘤及少突-星形细胞起源肿瘤染色体1p /19q杂合性缺失与人IDH1-R132H突变蛋白表达的相关性，探索预测少突胶质细胞起源肿瘤及少突-星形细胞起源肿瘤化疗敏感性的分子标志物。

方法

选择病理学诊断为各类型和级别的少突胶质细胞起源肿瘤及少突-星形细胞起源肿瘤75例，采用荧光原位杂交方法检测染色体1p/19q 杂合性缺失，免疫组织化学法检测其IDH1-R132H突变蛋白表达。

结果

75 例少突胶质细胞起源肿瘤及少突-星形细胞起源肿瘤1p/19q 杂合性缺失为37例(37/75，49.3%)，其中34例1p和19q同时发生缺失，1p缺失与19q缺失二者密切相关(P<0.01)。在少突胶质细胞瘤(WHO Ⅱ级)中，1p/19q 杂合性缺失检出率比间变型少突胶质细胞瘤(WHOⅢ级)高，但差异无显著性。少突胶质细胞起源肿瘤(WHOⅡ级和WHOⅢ 级)中1p/19q杂合性缺失率高于少突-星形细胞起源肿瘤(WHOⅡ级和WHOⅢ级)(P<0.05)。而且少突胶质细胞起源肿瘤中1p/19q 杂合性缺失均为联合缺失，1p和19q的单独缺失仅发生在少突- 星形细胞起源肿瘤中。在75例中51例(68.0%)少突胶质细胞起源肿瘤及少突-星形细胞起源肿瘤出现IDH1-R132H突变蛋白表达。少突胶质细胞起源肿瘤IDH1-R132H突变蛋白检测阳性率高于少突- 星形细胞起源肿瘤。而且少突胶质细胞起源肿瘤及少突-星形细胞起源肿瘤中，IDH1突变蛋白阳性表达与染色体1p/19q 杂合性缺失均有明显相关性 (P<0.05)。

结论

IDH1-R132H突变蛋白表达是预测少突胶质细胞起源肿瘤及少突-星形细胞起源肿瘤1p /19q 是否杂合性缺失的潜在分子标志物。

【关键词】少突胶质细胞起源肿瘤; 少突-星形细胞起源肿瘤;1p /19q; 异柠檬酸脱氢酶-1; 相关性

[ A b s t r a c t ] Objective To observe the correlation between delection of chromosome 1p/19q and expression of R132H mutant IDH1 status in oligodendroglial tumors, and to explore the molecular markers forecasting chemosensitivity of oligodendroglial tumors. Methods 75 ol igodendrogl ial tumors (38 oligodendrogliomas and 37 oligoastrocytomas). Immunohistochemistry method was used to detect the expression of R132H mutant IDH1 protein， and fluorescence in situ hybridization was carried out to detect the 1p /19q deletion. Results The FISH studies demonstrated that delection of chromosome 1p/19q was in 37 cases(37/75, 49.3%), of which co-deletion were detected in 34 cases.1p and 19q LOH were closely correlated (P<0.01). In oligodendrogliomas (WHOⅡ) cases the deletion rate was slightly higher than in oligodendrogliomas (WHO Ⅲ) cases. There were no statistically significant differences. In oligodendrogliomas (WHO Ⅱand WHOⅢ) cases the deletion rate of chromosome 1p/19q was higher than in oligoastrocytomas (WHOⅡand WHO Ⅲ) cases (P<0.05).The deletion in oligodendrogliomas were all combined deletion, and 1p single deletion and 19q single deletion were only found in oligoastrocytomas. In the 75 cases，the expression of R132H mutant IDH1 was positive in 51 cases，which accounted for 68.0%.In oligodendrogliomas the expression of R132H mutant IDH1 was higher than in oligoastrocytomas. The statistical analysis indicated that there was a correlation between the expression of R132H mutant IDH1 protein and the 1p /19q combined deletion in oligodendrogliomas (P<0.05). Conclusion 132H mutant IDH1 protein is the potential molecular marker forecasting the status of 1p /19q deletion in oligodendrogliomas.
[ K e y w o r d s ] o l i g o d e n d r o g l i oma s , oligoastrocytomas,1p/19q, IDH1, correlation