少突胶质细胞起源肿瘤及少突-星形细胞起源肿瘤中1p/19q杂合性缺失与IDH1-R132H突变蛋白表达的相关性

Correlation of chromosome 1p and 19q status and expression of R132H mutant IDH1 protein in oligodendroglial tumors

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38例及少突-星形细胞起源肿瘤37例,共75例,采用荧光原位杂交方法检测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（WHOⅡ级）中,1p/19q杂合性缺失检出率比间变性少突胶质细胞瘤（WHOⅢ级）高,但差异无统计学意义（P＞0.05）.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-R132H突变蛋白阳性表达与1p/19q杂合性缺失均有明显相关性（P＜0.05）.结论 IDH1-R132H突变蛋白表达与1p/19q杂合性缺失有明显相关性,IDH1-R132H蛋白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.

Objective To correlate the presence of chromosome 1p/19q deletion with the expression of R132H mutant IDH1 status in oligodendroglial tumors,and to explore molecular markers for predicting chemosensitivity of oligodendroglial tumors.Methods The study included 75 oligodendroglial tumors （38 oligodendrogliomas and 37 oligoastrocytomas）.Immunohistochemistry was used to detect the expression of R132H mutant IDH1 protein,and fluorescence in situ hybridization （FISH） was employed to detect 1p/19q deletion.Results Deletion of chromosome 1p and/or 19q was detected in 37 cases（37/75,49.3％）,among which co-deletion of 1p and 19q was seen in 34 cases （closely correlated,P ＜ 0.01）.Oligodendrogliomas WHO Ⅱ had a slightly higher deletion rate than oligodendrogliomas WHO Ⅲ,although without statistical significance.Oligodendrogliomas WHO Ⅱ and WHO Ⅲ had a significantly higher deletion rate of chromosome 1p/19q than oligoastrocytomas WHO Ⅱ and WHO Ⅲ （P ＜0.05）.While combined loss of 1p/19q was always detected in oligodendrogliomas when FISH was positive,isolated 1p or 19q deletion was only found in oligoastrocytomas.The expression of R132H mutant IDH1 was detected in 51 of 75 cases （68.0％）,in which oligodendrogliomas had a higher positive rate than oligoastrocytomas.Statistical analysis demonstrated a significant correlation between the expression of R132H mutant IDH1 protein and the presence of combined 1p/19q deletion in oligodendrogliomas （P ＜ 0.05）.Conclusions A significant correlation was observed between the expression of R132H mutant protein and 1p/19q LOH.Expression of 132H mutant IDH1 protein is the potential biomarker for predicating the presence of 1p/19q deletion in oligodendrogliomas.