TY - JOUR
T1 - Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium
AU - Takami, Hirokazu
AU - Fukuoka, Kohei
AU - Fukushima, Shintaro
AU - Nakamura, Taishi
AU - Mukasa, Akitake
AU - Saito, Nobuhito
AU - Yanagisawa, Takaaki
AU - Nakamura, Hideo
AU - Sugiyama, Kazuhiko
AU - Kanamori, Masayuki
AU - Tominaga, Teiji
AU - Maehara, Taketoshi
AU - Nakada, Mitsutoshi
AU - Kanemura, Yonehiro
AU - Asai, Akio
AU - Takeshima, Hideo
AU - Hirose, Yuichi
AU - Iuchi, Toshihiko
AU - Nagane, Motoo
AU - Yoshimoto, Koji
AU - Matsumura, Akira
AU - Kurozumi, Kazuhiko
AU - Nakase, Hiroyuki
AU - Sakai, Keiichi
AU - Tokuyama, Tsutomu
AU - Shibui, Soichiro
AU - Nakazato, Yoichi
AU - Narita, Yoshitaka
AU - Nishikawa, Ryo
AU - Matsutani, Masao
AU - Ichimura, Koichi
N1 - Funding Information:
This study was supported by a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan.
Funding Information:
Conflict of interest statement. Koichi Ichimura received a research grant from EPS Corporation. The other authors declare no conflicts of interest related to this work.
Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1093/neuonc/noz139
DO - 10.1093/neuonc/noz139
M3 - Article
C2 - 31420671
AN - SCOPUS:85076876510
VL - 21
SP - 1565
EP - 1577
JO - Neuro-Oncology
JF - Neuro-Oncology
SN - 1522-8517
IS - 12
ER -
