Journal
LABORATORY INVESTIGATION
Volume 102, Issue 2, Pages 126-133Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/s41374-021-00667-6
Keywords
-
Categories
Ask authors/readers for more resources
The 5th edition of WHO Classification of Tumors of the Central Nervous System incorporated new molecular markers for IDH-mutant and -wild-type astrocytoma, aiming to improve risk stratification. However, challenges and debates persist in the grading of gliomas, particularly regarding the utilization of histological and proliferative markers.
The 5th edition of WHO Classification of Tumors of the Central Nervous System adopted new molecular markers into the revised grading criteria of IDH-mutant and -wild-type astrocytoma, i.e., the CDKN2A/B homozygous deletion for IDH-mutant astrocytoma and the following three criteria for IDH-wild-type astrocytoma: the concurrent gain of whole chromosome 7 and loss of whole chromosome 10, TERT promoter mutations, and EGFR amplification, as independent molecular markers of the highest grade. The grading of gliomas based on histological features has been a subject of debate for several decades. A consensus has not yet been reached because of technical limitations and inter-observer variations. While the traditional grading system has failed to stratify the risk of IDH-mutant astrocytoma, canonical histological and proliferative markers may be applicable to the risk stratification of IDH-wild-type astrocytoma. Numerous studies have examined molecular markers in order to obtain more clinically relevant information that will improve the risk stratification of gliomas. The CDKN2A/B homozygous deletion for IDH-mutant astrocytoma and the following three criteria for IDH-wild-type astrocytoma: the concurrent gain of whole chromosome 7 and loss of whole chromosome 10, TERT promoter mutations, and EGFR amplification, were identified as independent molecular markers of the worst clinical outcomes. Therefore, the 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System adopted these molecular markers into the revised grading criteria of IDH-mutant and -wild-type astrocytoma, respectively, as a grading system within tumor types. Of note, several recent studies have shown that some low-grade IDH-wild-type astrocytoma lacking both the molecular glioblastoma signature and genetic alterations typical of pediatric-type gliomas may demonstrate a relatively indolent clinical course, suggesting the existence of lower-grade adult IDH-wild-type astrocytoma. In terms of oligodendroglioma, IDH-mutant, and 1p/19q codeleted, consistent makers that predict poor outcomes have not yet been identified, and, thus, the current criteria have remained unchanged. Molecular testing to fulfill the revised WHO criteria is, however, not always available worldwide, and in that case, an integrated diagnosis combining all available complementary information is highly recommended. This review discusses controversial issues surrounding legacy grading systems and newly identified potential genetic markers of adult diffuse gliomas and provides perspectives on future grading systems.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available