Sabit Hemragul, Nakada Mitsutoshi, Furuta Takuya, Watanabe Takuya, Hayashi Yutaka, Sato Hiroshi, Kato Yukinari, Hamada Jun-ichiro
Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
Brain Tumor Pathol. 2014 Oct;31(4):242-6. doi: 10.1007/s10014-013-0172-y. Epub 2014 Jan 3.
Glioma, the most common primary brain tumor, is characterized by proliferative-invasive growth. However, the detailed biological characteristics of invading glioma cells remain to be elucidated. A monoclonal antibody (clone HMab-1) that specifically and sensitively recognizes the isocitrate dehydrogenase-1 (IDH1) protein carrying the R132H mutation can identify invading glioma cells by immunostaining. To investigate the degree of invasion in gliomas of distinct grades and the proliferative capacity of the invading cells, immunofluorescent staining was conducted using antibodies against IDH1-R132H and Ki-67 on 11 surgical and autopsy specimens of the tumor core and the invading area. Higher numbers of IDH1-R132H-positive cells in the invading area correlated with a higher tumor grade. Double staining for IDH1-R132H and Ki-67 demonstrated that most invading cells that expressed IDH1-R132H were not stained by the Ki-67 antibody, and the ratio of Ki-67-positive cells among IDH1-R132H-positive cells was significantly lower in the invasion area than in the tumor core in all grades of glioma. These data suggest that higher grade gliomas have a greater invasive potential and that invading cells possess low proliferative capacity.
胶质瘤是最常见的原发性脑肿瘤,其特征为增殖性侵袭性生长。然而,侵袭性胶质瘤细胞的详细生物学特性仍有待阐明。一种单克隆抗体(克隆号HMab-1)能特异性且灵敏地识别携带R132H突变的异柠檬酸脱氢酶-1(IDH1)蛋白,通过免疫染色可识别侵袭性胶质瘤细胞。为研究不同分级胶质瘤的侵袭程度以及侵袭细胞的增殖能力,我们使用抗IDH1-R132H和Ki-67抗体,对11例手术及尸检标本的肿瘤核心和侵袭区域进行了免疫荧光染色。侵袭区域中IDH1-R132H阳性细胞数量越多,肿瘤分级越高。IDH1-R132H和Ki-67的双重染色显示,大多数表达IDH1-R132H的侵袭细胞未被Ki-67抗体染色,且在所有分级的胶质瘤中,侵袭区域IDH1-R132H阳性细胞中Ki-67阳性细胞的比例显著低于肿瘤核心。这些数据表明,高级别胶质瘤具有更大的侵袭潜能,且侵袭细胞的增殖能力较低。