Cargando…

GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM

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 Consortium were reviewed. A total of 190 cases were classified as primar...

Descripción completa

Detalles Bibliográficos
Autores principales: Takami, Hirokazu, Ichimura, Koichi, Fukuoka, Kohei, Mukasa, Akitake, Saito, Nobuhito, Narita, Yoshitaka, Shibui, Soichiro, Nakazato, Yoichi, Nishikawa, Ryo, Matsutani, Masao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715272/
http://dx.doi.org/10.1093/neuonc/noaa222.235
_version_ 1783618916260511744
author Takami, Hirokazu
Ichimura, Koichi
Fukuoka, Kohei
Mukasa, Akitake
Saito, Nobuhito
Narita, Yoshitaka
Shibui, Soichiro
Nakazato, Yoichi
Nishikawa, Ryo
Matsutani, Masao
author_facet Takami, Hirokazu
Ichimura, Koichi
Fukuoka, Kohei
Mukasa, Akitake
Saito, Nobuhito
Narita, Yoshitaka
Shibui, Soichiro
Nakazato, Yoichi
Nishikawa, Ryo
Matsutani, Masao
author_sort Takami, Hirokazu
collection PubMed
description 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 Consortium were reviewed. A total of 190 cases were classified as primary 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 PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and 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: These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.
format Online
Article
Text
id pubmed-7715272
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-77152722020-12-09 GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM Takami, Hirokazu Ichimura, Koichi Fukuoka, Kohei Mukasa, Akitake Saito, Nobuhito Narita, Yoshitaka Shibui, Soichiro Nakazato, Yoichi Nishikawa, Ryo Matsutani, Masao Neuro Oncol Germ Cell Tumors 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 Consortium were reviewed. A total of 190 cases were classified as primary 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 PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and 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: These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor. Oxford University Press 2020-12-04 /pmc/articles/PMC7715272/ http://dx.doi.org/10.1093/neuonc/noaa222.235 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Germ Cell Tumors
Takami, Hirokazu
Ichimura, Koichi
Fukuoka, Kohei
Mukasa, Akitake
Saito, Nobuhito
Narita, Yoshitaka
Shibui, Soichiro
Nakazato, Yoichi
Nishikawa, Ryo
Matsutani, Masao
GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
title GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
title_full GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
title_fullStr GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
title_full_unstemmed GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
title_short GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
title_sort gct-15. integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the igct consortium
topic Germ Cell Tumors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715272/
http://dx.doi.org/10.1093/neuonc/noaa222.235
work_keys_str_mv AT takamihirokazu gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT ichimurakoichi gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT fukuokakohei gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT mukasaakitake gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT saitonobuhito gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT naritayoshitaka gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT shibuisoichiro gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT nakazatoyoichi gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT nishikawaryo gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium
AT matsutanimasao gct15integratedclinicalhistopathologicalandmoleculardataanalysisof190centralnervoussystemgermcelltumorsfromtheigctconsortium