TY - JOUR
T1 - Overcoming the Odds
T2 - Toward a molecular profile of long-term survival in glioblastoma
AU - Richardson, Timothy E.
AU - Kumar, Ashwani
AU - Xing, Chao
AU - Hatanpaa, Kimmo J.
AU - Walker, Jamie M.
N1 - Publisher Copyright:
© 2020 American Association of Neuropathologists, Inc. All rights reserved.
PY - 2021
Y1 - 2021
N2 - For over a century, gliomas were characterized solely by histologic features. With the publication of the WHO Classification of Tumours of the Central Nervous System, Revised 4th Edition in 2016, integrated histologic and molecular diagnosis became the norm, providing improved tumor grading and prognosis with IDH1/ 2 (isocitrate dehydrogenase 1 and 2) mutation being the most significant prognostic feature in all grades of adult diffuse glioma. Since then, much work has been done to identify additional molecular prognostic features, but the bulk of the progress has been made in defining aggressive features in lower grade astrocytoma. Although there have been several large case series of glioblastomas with long-term survival (LTS; overall survival >36 months), less is known about the clinical and molecular features of these cases. Herein, we review 19 studies examining LTS glioblastoma patients from 2009 to 2020 that include variable molecular analysis, including 465 cases with survival of 36 months or more (total n ¼ 2328). These studies suggest that while there is no definitive molecular signature of long survival, younger age, IDH mutation, and MGMT (methyl guanine methyl transferase) promoter hypermethylation are associated with longer overall survival, and in IDH-wildtype tumors, chromosome 19/20 co-gain and lack of EGFR amplification, chromosome 7 gain/ 10 loss, and TERT promoter mutation are associated with LTS.
AB - For over a century, gliomas were characterized solely by histologic features. With the publication of the WHO Classification of Tumours of the Central Nervous System, Revised 4th Edition in 2016, integrated histologic and molecular diagnosis became the norm, providing improved tumor grading and prognosis with IDH1/ 2 (isocitrate dehydrogenase 1 and 2) mutation being the most significant prognostic feature in all grades of adult diffuse glioma. Since then, much work has been done to identify additional molecular prognostic features, but the bulk of the progress has been made in defining aggressive features in lower grade astrocytoma. Although there have been several large case series of glioblastomas with long-term survival (LTS; overall survival >36 months), less is known about the clinical and molecular features of these cases. Herein, we review 19 studies examining LTS glioblastoma patients from 2009 to 2020 that include variable molecular analysis, including 465 cases with survival of 36 months or more (total n ¼ 2328). These studies suggest that while there is no definitive molecular signature of long survival, younger age, IDH mutation, and MGMT (methyl guanine methyl transferase) promoter hypermethylation are associated with longer overall survival, and in IDH-wildtype tumors, chromosome 19/20 co-gain and lack of EGFR amplification, chromosome 7 gain/ 10 loss, and TERT promoter mutation are associated with LTS.
KW - 19þ/20þ
KW - 7þ/10-
KW - CCND2
KW - EGFR
KW - IDH mutation
KW - MGMT
KW - TERT
UR - http://www.scopus.com/inward/record.url?scp=85091265215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091265215&partnerID=8YFLogxK
U2 - 10.1093/JNEN/NLAA102
DO - 10.1093/JNEN/NLAA102
M3 - Review article
C2 - 32954439
AN - SCOPUS:85091265215
SN - 0022-3069
VL - 79
SP - 1031
EP - 1037
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 10
ER -