Ogura Ryosuke, Tsukamoto Yoshihiro, Natsumeda Manabu, Isogawa Mizuho, Aoki Hiroshi, Kobayashi Tsutomu, Yoshida Seiichi, Okamoto Kouichiro, Takahashi Hitoshi, Fujii Yukihiko, Kakita Akiyoshi
Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.
Neuropathology. 2015 Aug;35(4):324-35. doi: 10.1111/neup.12196. Epub 2015 May 6.
Genetic and epigenetic status, including mutations of isocitrate dehydrogenase (IDH) and TP53 and methylation of O(6) -methylguanine-DNA methyltransferase (MGMT), are associated with the development of various types of glioma and are useful for prognostication. Here, using routinely available histology sections from 312 patients with diffuse gliomas, we performed immunohistochemistry using antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53 expression to evaluate the possible prognostic significance of these features. With regard to overall survival (OS), univariate analysis indicated that an IDH1-positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative profile in patients with GBM and AA were significantly associated with a favorable outcome. Multivariate analysis revealed that both profiles were independent factors influencing prognosis. The OS of patients with IDH1-positive/MGMT-negative profiles was significantly longer than that of patients with negative/negative and negative/positive profiles. A p53 profile was not an independent prognostic factor. However, for GBM/AA patients with IDH1-negative/MGMT-negative profiles, p53 overexpression was significantly associated with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT and p53 profiles may be useful for prognostication of GBM/AA.
遗传和表观遗传状态，包括异柠檬酸脱氢酶（IDH）和TP53的突变以及O(6)-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的甲基化，与各种类型胶质瘤的发生发展相关，并且对预后评估有帮助。在此，我们使用312例弥漫性胶质瘤患者常规获取的组织学切片，采用针对IDH1突变、MGMT甲基化状态和异常p53表达的特异性抗体进行免疫组化，以评估这些特征可能的预后意义。关于总生存期（OS），单因素分析表明，胶质母细胞瘤（GBM）、间变性星形细胞瘤（AA）、间变性少突星形细胞瘤和少突胶质细胞瘤患者的IDH1阳性特征，或GBM和AA患者的MGMT阴性特征与良好预后显著相关。多因素分析显示，这两种特征都是影响预后的独立因素。IDH1阳性/MGMT阴性特征患者的OS显著长于阴性/阴性和阴性/阳性特征的患者。p53特征不是独立的预后因素。然而，对于IDH1阴性/MGMT阴性特征的GBM/AA患者，p53过表达与不良预后显著相关。因此，IDH1和MGMT的免疫组化特征在胶质瘤中具有重要意义，IDH1、MGMT和p53特征的联合可能有助于GBM/AA的预后评估。
