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首都醫(yī)科大學(xué)三博腦科醫(yī)院病理科 姚坤 段澤君 邊宇 馬忠 齊雪嶺

【摘要】目的 觀察少突膠質(zhì)細(xì)胞起源腫瘤及少突-星形細(xì)胞起源腫瘤染色體1p /19q雜合性缺失與人IDH1-R132H突變蛋白表達(dá)的相關(guān)性，探索預(yù)測(cè)少突膠質(zhì)細(xì)胞起源腫瘤及少突-星形細(xì)胞起源腫瘤化療敏感性的分子標(biāo)志物。

方法

選擇病理學(xué)診斷為各類型和級(jí)別的少突膠質(zhì)細(xì)胞起源腫瘤及少突-星形細(xì)胞起源腫瘤75例，采用熒光原位雜交方法檢測(cè)染色體1p/19q 雜合性缺失，免疫組織化學(xué)法檢測(cè)其IDH1-R132H突變蛋白表達(dá)。

結(jié)果

75 例少突膠質(zhì)細(xì)胞起源腫瘤及少突-星形細(xì)胞起源腫瘤1p/19q 雜合性缺失為37例(37/75，49.3%)，其中34例1p和19q同時(shí)發(fā)生缺失，1p缺失與19q缺失二者密切相關(guān)(P<0.01)。在少突膠質(zhì)細(xì)胞瘤(WHO Ⅱ級(jí))中，1p/19q 雜合性缺失檢出率比間變型少突膠質(zhì)細(xì)胞瘤(WHOⅢ級(jí))高，但差異無(wú)顯著性。少突膠質(zhì)細(xì)胞起源腫瘤(WHOⅡ級(jí)和WHOⅢ 級(jí))中1p/19q雜合性缺失率高于少突-星形細(xì)胞起源腫瘤(WHOⅡ級(jí)和WHOⅢ級(jí))(P<0.05)。而且少突膠質(zhì)細(xì)胞起源腫瘤中1p/19q 雜合性缺失均為聯(lián)合缺失，1p和19q的單獨(dú)缺失僅發(fā)生在少突- 星形細(xì)胞起源腫瘤中。在75例中51例(68.0%)少突膠質(zhì)細(xì)胞起源腫瘤及少突-星形細(xì)胞起源腫瘤出現(xiàn)IDH1-R132H突變蛋白表達(dá)。少突膠質(zhì)細(xì)胞起源腫瘤IDH1-R132H突變蛋白檢測(cè)陽(yáng)性率高于少突- 星形細(xì)胞起源腫瘤。而且少突膠質(zhì)細(xì)胞起源腫瘤及少突-星形細(xì)胞起源腫瘤中，IDH1突變蛋白陽(yáng)性表達(dá)與染色體1p/19q 雜合性缺失均有明顯相關(guān)性 (P<0.05)。

結(jié)論

IDH1-R132H突變蛋白表達(dá)是預(yù)測(cè)少突膠質(zhì)細(xì)胞起源腫瘤及少突-星形細(xì)胞起源腫瘤1p /19q 是否雜合性缺失的潛在分子標(biāo)志物。

【關(guān)鍵詞】少突膠質(zhì)細(xì)胞起源腫瘤; 少突-星形細(xì)胞起源腫瘤;1p /19q; 異檸檬酸脫氫酶-1; 相關(guān)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