Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
J Neurooncol. 2021 Dec;155(3):235-246. doi: 10.1007/s11060-021-03855-y. Epub 2021 Oct 31.
Lower grade gliomas with 1p/19q codeletion are often responsive to chemotherapy, and several of these have been treated using upfront chemotherapy and subsequent resection following tumor volume decrease. This study aimed to elucidate the histological changes and the mechanism of recurrence after alkylating agent chemotherapy in 1p/19-codeleted gliomas.
Fourteen 1p/19q-codeleted gliomas resected following tumor volume decrease after alkylating agent chemotherapy were included and compared with their pre-chemotherapy specimens. Histological changes were investigated using hematoxylin-eosin staining, and changes in proliferative activity, status of glioma stem cells (GSCs), and tumor-infiltrating macrophages were assessed using immunohistochemistry for Ki-67/MIB-1, CD68 as a pan-macrophage/monocyte marker, CD163 as a presumed marker of M2 polarity, and nestin and CD133 as markers of GSCs.
The most frequent histological findings following chemotherapy included a sparse glial background and abundant foamy cell infiltration. The Ki-67/MIB-1 index decreased and the number of CD68 + cells increased after chemotherapy. The increasing rate of CD68 + cells in the post-/pre-chemotherapy specimens was inversely correlated with patient prognosis but not tumor response. The number of CD163 + cells, M2/M1 + M2 ratio, and the ratio of GSCs to total tumor cells increased after chemotherapy, and those in the post-chemotherapy specimens were negatively correlated with patient prognosis. There was a correlation between the M2/M1 + M2 ratio and the ratio of GSCs in both pre- and post-chemotherapy specimens.
GSCs in conjunction with M2 macrophages constitute the mechanism of resistance to and recurrence after alkylating agent chemotherapy in 1p/19q-codeleted gliomas.
1p/19q 联合缺失型低级别胶质瘤对化疗敏感，其中一些患者接受了初始化疗，待肿瘤体积缩小后再行手术切除。本研究旨在阐明 1p/19q 联合缺失型胶质瘤经烷化剂化疗后肿瘤体积缩小并复发的组织学变化和机制。
本研究纳入了 14 例经烷化剂化疗肿瘤体积缩小后行手术切除的 1p/19q 联合缺失型胶质瘤患者，并与化疗前标本进行比较。采用苏木精-伊红染色观察组织学变化，通过免疫组织化学法检测 Ki-67/MIB-1、CD68（作为一种巨噬细胞/单核细胞的通用标志物）、CD163（作为 M2 极性的假定标志物）、巢蛋白和 CD133（作为神经干细胞标志物），评估增殖活性、神经干细胞状态和肿瘤浸润巨噬细胞的变化。
化疗后最常见的组织学表现为稀疏的神经胶质背景和丰富的泡沫状细胞浸润。化疗后 Ki-67/MIB-1 指数降低，CD68 阳性细胞数量增加。化疗后 CD68 阳性细胞的增加率与患者预后呈负相关，但与肿瘤反应无关。化疗后 CD163 阳性细胞、M2/M1+M2 比值和神经干细胞与总肿瘤细胞的比值增加，且这些指标在化疗后标本中与患者预后呈负相关。化疗前后标本中 M2/M1+M2 比值与神经干细胞数量呈正相关。
GSCs 与 M2 巨噬细胞共同构成了 1p/19q 联合缺失型胶质瘤对烷化剂化疗耐药和复发的机制。
