Lee Sang Hyuk, Kim Tae Gyu, Ryu Kyeong Hwa, Kim Seok Hyun, Kim Young Zoon
Division of Neuro Oncology and Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea.
Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea.
Biomedicines. 2024 Oct 4;12(10):2256. doi: 10.3390/biomedicines12102256.
: We primarily investigated the prognostic role of homozygous deletion in CNS WHO grade 4 gliomas. Additionally, we plan to examine traditional prognostic factors for grade 4 gliomas and validate the findings. : We conducted a retrospective analysis of the glioma cohorts at our institute. We reviewed medical records spanning a 15-year period and examined pathological slides for an updated diagnosis according to the 2021 WHO classification of CNS tumors. We examined the mutation and deletion using NGS analysis with ONCOaccuPanel. Further, we examined traditional prognostic factors, including age, WHO performance status, extent of resection, and promoter methylation status. : The mean follow-up duration was 27.5 months (range: 4.1-43.5 months) and mean overall survival (OS) was 20.7 months (SD, ±1.759). After the exclusion of six patients with a poor status of pathologic samples, a total of 136 glioblastoma cases diagnosed by previous WHO classification criteria were newly classified into 29 (21.3%) astrocytoma, -mutant, and CNS WHO grade 4 cases, and 107 (78.7%) glioblastoma, -wildtype, and CNS WHO grade 4 cases. Among them, 61 (56.0%) had deletions. The high-risk group with deletion regardless of mutation had a mean OS of 16.65 months (SD, ±1.554), the intermediate-risk group without deletion and with mutation had a mean OS of 21.85 months (SD, ±2.082), and the low-risk group without CDKN2A deletion and with mutation had a mean OS of 33.38 months (SD, ±2.946). Multifactor analysis showed that age (≥50 years vs. <50 years; HR 4.645), WHO performance (0, 1 vs. 2; HR 5.002), extent of resection (gross total resection vs. others; HR 5.528), promoter methylation, (methylated vs. unmethylated; HR 5.078), mutation (mutant vs. wildtype; HR 6.352), and deletion (absence vs. presence; HR 13.454) were associated with OS independently. : The present study suggests that deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant , they may have poor clinical outcomes because of deletion.
我们主要研究了纯合缺失在中枢神经系统WHO 4级胶质瘤中的预后作用。此外，我们计划检查4级胶质瘤的传统预后因素并验证研究结果。我们对我院的胶质瘤队列进行了回顾性分析。我们查阅了15年期间的病历，并根据2021年WHO中枢神经系统肿瘤分类检查病理切片以进行更新诊断。我们使用ONCOaccuPanel通过NGS分析检测了突变和缺失。此外，我们还检查了传统预后因素，包括年龄、WHO体能状态、切除范围和启动子甲基化状态。平均随访时间为27.5个月（范围：4.1 - 43.5个月），平均总生存期（OS）为20.7个月（标准差，±1.759）。在排除6例病理样本状态不佳的患者后，共有136例根据先前WHO分类标准诊断的胶质母细胞瘤病例被重新分类为29例（21.3%）星形细胞瘤、-突变型和中枢神经系统WHO 4级病例，以及107例（78.7%）胶质母细胞瘤、-野生型和中枢神经系统WHO 4级病例。其中，61例（56.0%）存在缺失。无论是否有突变，存在缺失的高危组平均OS为16.65个月（标准差，±1.554），无缺失且有突变的中危组平均OS为21.85个月（标准差，±2.082），无CDKN2A缺失且有突变的低危组平均OS为33.38个月（标准差，±2.946）。多因素分析显示，年龄（≥50岁与<50岁；HR 4.645）、WHO体能状态（0、1与2；HR 5.002）、切除范围（全切与其他；HR 5.528）、启动子甲基化（甲基化与未甲基化；HR 5.078）、突变（突变型与野生型；HR 6.352）和缺失（无与有；HR 13.454）均独立与OS相关。本研究表明，缺失在中枢神经系统WHO 4级胶质瘤中具有强大的预后作用。即使中枢神经系统WHO 4级胶质瘤有突变，由于缺失它们可能仍具有较差的临床结局。
