Department of Pathology, Odense University Hospital, Odense, Denmark.
Department of Oncology, Odense University Hospital, Odense, Denmark.
Sci Rep. 2021 Sep 9;11(1):17918. doi: 10.1038/s41598-021-95958-9.
Survival of glioblastoma patients varies and prognostic markers are important in the clinical setting. With digital pathology and improved immunohistochemical multiplexing becoming a part of daily diagnostics, we investigated the prognostic value of the Ki-67 labelling index (LI) in glioblastomas more precisely than previously by excluding proliferation in non-tumor cells from the analysis. We investigated the Ki-67 LI in a well-annotated population-based glioblastoma patient cohort (178 IDH-wildtype, 3 IDH-mutated). Ki-67 was identified in full tumor sections with automated digital image analysis and the contribution from non-tumor cells was excluded using quantitative double-immunohistochemistry. For comparison of the Ki-67 LI between WHO grades (II-IV), 9 IDH-mutated diffuse astrocytomas and 9 IDH-mutated anaplastic astrocytomas were stained. Median Ki-67 LI increased with increasing WHO grade (median 2.7%, 6.4% and 27.5%). There was no difference in median Ki-67 LI between IDH-mutated and IDH-wildtype glioblastomas (p = 0.9) and Ki-67 LI was not associated with survival in glioblastomas in neither univariate (p = 0.9) nor multivariate analysis including MGMT promoter methylation status and excluding IDH-mutated glioblastomas (p = 0.2). Ki-67 may be of value in the differential diagnostic setting, but it must not be over-interpreted in the clinico-pathological context.
胶质母细胞瘤患者的生存率存在差异，预后标志物在临床环境中很重要。随着数字病理学和免疫组化多重技术的改进成为日常诊断的一部分，我们通过排除分析中非肿瘤细胞的增殖，比以前更精确地研究了 Ki-67 标记指数 (LI) 在胶质母细胞瘤中的预后价值。我们在一个有充分注释的基于人群的胶质母细胞瘤患者队列（178 例 IDH 野生型，3 例 IDH 突变型）中研究了 Ki-67 LI。使用自动化数字图像分析在全肿瘤切片中识别 Ki-67，并使用定量双免疫组化排除非肿瘤细胞的贡献。为了比较 WHO 分级（II-IV）之间的 Ki-67 LI，对 9 例 IDH 突变型弥漫性星形细胞瘤和 9 例 IDH 突变型间变性星形细胞瘤进行了染色。Ki-67 LI 随 WHO 分级的增加而增加（中位数分别为 2.7%、6.4%和 27.5%）。IDH 突变型和 IDH 野生型胶质母细胞瘤之间的 Ki-67 LI 中位数无差异（p=0.9），Ki-67 LI 与胶质母细胞瘤的生存无关，无论是单变量分析（p=0.9）还是包括 MGMT 启动子甲基化状态和排除 IDH 突变型胶质母细胞瘤的多变量分析（p=0.2）。Ki-67 在鉴别诊断中可能有价值，但在临床病理环境中不能过度解释。
