Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium
Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium
复制标题
DOI：
10.1093/neuonc/noz139
复制
发表时间：
2019-12-01
期刊：
影响因子：
15.9
通讯作者：
Ichimura, Koichi
中科院分区：
文献类型：
--
作者：
Takami, Hirokazu;Fukuoka, Kohei;Ichimura, Koichi
背景我们整合了中枢神经系统生殖细胞肿瘤的临床、组织病理学和分子生物学数据，以提供对其管理的见解。对来自颅内生殖细胞肿瘤基因组分析（iGCT）联盟的数据进行了审查。根据中心病理回顾，共190例患者被归类为原发性生殖细胞肿瘤（GCT）。除1例双灶性（神经垂体和松果体）和包括神经垂体或松果体在内的多发性病变外，所有病例均为生殖细胞瘤（34/35）。生殖细胞瘤患者的年龄明显高于其他组织学类型。肿瘤标志物和组织病理学诊断之间的比较显示，18.2%的组织病理学诊断的生殖细胞瘤的标志物阳性和6.1%的非生殖细胞瘤GCT的标志物阴性，这表明在使用标记物或组织病理学单独使用小标本进行诊断的局限性。局部和中心组织病理学诊断之间的比较显示12.7%的不一致性。不一致性在活检病例中的发生率明显较低，这意味着难以检测异质性GCT的所有组织病理学成分。典型部位（神经垂体或松果体）生殖细胞瘤的无进展生存率高于非典型部位生殖细胞瘤（P = 0.03）。一项分子临床关联研究显示，男性中经常发生有丝分裂原活化蛋白激酶（MAPK）途径突变（51.4% vs 14.3%，P = 0.007），基底神经节病例中经常发生磷脂酰肌醇-3激酶/哺乳动物雷帕霉素靶蛋白（PI 3 K/mTOR）途径突变（P = 0.004）。基底神经节病例也有频繁的染色体丢失。某些染色体异常（2 q、8 q增加、5 q、9 p/q、13 q、15 q丢失）具有潜在的预后意义。本研究关于临床和分子异质性的深入发现将增加我们对这种神秘肿瘤发病机制的理解。
Background. We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.Methods. Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews.Results. All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.Conclusions. The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.