Deb Prabal, Mani N S, Sudumbrekar S M, Taneja Nitin, Patrikar Seema
Associate Professor, Department of Pathology, AFMC, Pune-411040, India.
DDG, MS (P), O/o DGMS (Army), Army Headquarter, New Delhi, India.
Med J Armed Forces India. 2013 Jul;69(3):228-36. doi: 10.1016/j.mjafi.2012.08.030. Epub 2012 Dec 1.
Loss of heterozygosity (LOH)1p/19q, and epigenetic silencing of O(6)-methylguanine-DNAmethyltransferase (MGMT) gene, displayed promising role as predictive and prognostic markers in brain tumours. The present study correlated both with conventional histomorphologic prognostic markers and proliferative index in diffusely infiltrating gliomas (DIG).
Tissues from 45 patients were evaluated for LOH1p/19q using polymerase chain reaction based microsatellite analysis; and for MGMT using immunohistochemistry. Results were correlated with age, histologic type, WHO grade, and proliferation index.
Mean MIB-1 LI showed significant correlation with tumour grade. MGMT-staining in grade II and IV tumours were 31.1% and 16.8%, respectively, while in DA and GBM it was 88.2% and 19.0%, respectively, which were statistically significant. Sixteen cases showed LOH 1p and/or 19q of which 10 (5 oligodendroglial, 3 GBM, AA, DA) had combined LOH; while three each showed 1p (all GBM) and 19q (2 DA and GBM) loss. In the MIB-1LI ≤ 5% and >5% groups LOH 1p and/or 19q was encountered in 6 and 10 cases, respectively. A significant inverse association was noted between LOH with MGMT.
LOH1p/19q and MGMT shows good correlation with conventional histomorphologic and proliferation markers, and should constitute part of the optimal diagnostic workup of DIG.
1p/19q杂合性缺失（LOH）以及O(6)-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因的表观遗传沉默在脑肿瘤中作为预测和预后标志物显示出有前景的作用。本研究将二者与弥漫性浸润性胶质瘤（DIG）中的传统组织形态学预后标志物及增殖指数进行了相关性分析。
采用基于聚合酶链反应的微卫星分析对45例患者的组织进行1p/19q LOH评估；采用免疫组织化学法评估MGMT。结果与年龄、组织学类型、世界卫生组织分级及增殖指数进行相关性分析。
平均MIB-1标记指数与肿瘤分级显著相关。II级和IV级肿瘤中MGMT染色分别为31.1%和16.8%，而在间变性星形细胞瘤和胶质母细胞瘤中分别为88.2%和19.0%，差异具有统计学意义。16例显示1p和/或19q LOH，其中10例（5例少突胶质细胞瘤、3例胶质母细胞瘤、间变性星形细胞瘤、间变性少突胶质细胞瘤）存在联合LOH；3例分别显示1p缺失（均为胶质母细胞瘤）和19q缺失（2例间变性少突胶质细胞瘤和胶质母细胞瘤）。在MIB-1标记指数≤5%和>5%的组中，分别有6例和10例出现1p和/或19q LOH。LOH与MGMT之间存在显著的负相关。
1p/19q LOH和MGMT与传统组织形态学及增殖标志物显示出良好的相关性，应构成DIG最佳诊断检查的一部分。
