Hata Nobuhiro, Hatae Ryusuke, Yoshimoto Koji, Murata Hideki, Kuga Daisuke, Akagi Yojiro, Sangatsuda Yuhei, Suzuki Satoshi O, Iwaki Toru, Mizoguchi Masahiro, Iihara Koji
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Neurosurgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
Neuropathology. 2017 Jun;37(3):200-206. doi: 10.1111/neup.12362. Epub 2017 Jan 24.
Isocitrate dehydrogenase (IDH) mutation is a good prognostic marker for glioblastoma (GBM). Although it is infrequent in primary tumors, it is found in most lower-grade gliomas. Thus, it is unclear whether IDH mutation is a marker for a specific phenotype of apparently primary de novo GBMs (pGBMs), or a marker for secondary tumors (sGBMs). We addressed this issue by analyzing clinical, radiographic and molecular findings in our institutional case series. Our cases included 92 pGBMs, with five cases of IDH1 mutations at R132 and no IDH2 mutations. The median overall survival of these five patients was 29 months (range: 4 to >40 months), which is considered good prognoses. Clinical and radiographic characteristics were distinct from IDH-wildtype (IDH-wt) pGBMs. IDH-mutant (IDH-mut) tumors consistently involved insular lesions and were subdivided into: (i) the two cases of elderly patients with long clinical histories and features implying multistep tumor development; and (ii) the three cases of younger patients with diffusely swelling insular tumors, slight contrast enhancement and no necrosis. Genetic and expression analyses of IDH-mut pGBMs were similar to those of sGBMs, suggesting that they are indeed distinct from their IDH-wt counterparts. TERT promoter mutation, a genetic marker of oligodendroglial derivation, was detected in one long-surviving case, but genetic alterations in the astrocyte-sGBM pathway were generally prevalent in IDH-mut pGBMs. Our results present a unique phenotype of IDH-mut pGBMs arising from insular cortex region, the molecular backgrounds of which are similar to sGBMs.
异柠檬酸脱氢酶（IDH）突变是胶质母细胞瘤（GBM）的一个良好预后标志物。尽管它在原发性肿瘤中并不常见，但在大多数低级别胶质瘤中都能发现。因此，目前尚不清楚IDH突变是原发性新发GBM（pGBM）特定表型的标志物，还是继发性肿瘤（sGBM）的标志物。我们通过分析本机构病例系列中的临床、影像学和分子学发现来解决这个问题。我们的病例包括92例pGBM，其中5例存在R132位点的IDH1突变，未发现IDH2突变。这5例患者的中位总生存期为29个月（范围：4至>40个月），这被认为是良好的预后。其临床和影像学特征与IDH野生型（IDH-wt）pGBM不同。IDH突变型（IDH-mut）肿瘤始终累及岛叶病变，并可细分为：（i）2例老年患者，临床病史长，具有提示肿瘤多步骤发展的特征；（ii）3例年轻患者，岛叶肿瘤弥漫性肿胀，轻度强化且无坏死。IDH-mut pGBM的基因和表达分析与sGBM相似，表明它们确实与IDH-wt的pGBM不同。在1例长期存活的病例中检测到TERT启动子突变，这是少突胶质细胞起源的遗传标志物，但在IDH-mut pGBM中，星形胶质细胞-sGBM途径的基因改变普遍存在。我们的研究结果展示了一种起源于岛叶皮质区域的IDH-mut pGBM的独特表型，其分子背景与sGBM相似。
