Mismatch repair proteins PMS2 and MLH1 can further refine molecular stratification of IDH-mutant lower grade astrocytomas

The diagnostic role of Isocitrate Dehydrogenase (IDH) mutation status in adult lower grade astrocytomas was first formally presented within the WHO Classification of Tumours of the Central Nervous System (2016). IDH-mutant astrocytomas are not as common as IDH-wildtype astrocytomas but are of better...

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Published in:Clinical neurology and neurosurgery 2021-09, Vol.208, p.106882-106882, Article 106882
Main Authors: Yang, Rui Ryan, Li, Kay Ka-Wai, Zhang, Zhen-Yu, Chan, Aden Ka-Yin, Wang, Wei-Wei, Chan, Danny Tat-Ming, Li, Wen-Cai, Liu, Xian-Zhi, Li, Fang-Cheng, Chen, Hong, Ng, Ho-Keung, Mao, Ying, Shi, Zhi-Feng
Format: Article
Language:English
Subjects:
Adult
Antibodies
Astrocytoma
Astrocytoma - genetics
Astrocytoma - metabolism
Astrocytoma - mortality
Astrocytoma - pathology
Astrocytomas
Biomarkers, Tumor
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - mortality
Brain Neoplasms - pathology
Central nervous system
Copy number
Cyclin-dependent kinase 4
DNA repair
Female
Humans
Immunohistochemistry
Isocitrate dehydrogenase
Isocitrate Dehydrogenase - genetics
Isocitrate Dehydrogenase - metabolism
Male
Medical prognosis
Middle Aged
Mismatch repair
Mismatch Repair Endonuclease PMS2 - genetics
Mismatch Repair Endonuclease PMS2 - metabolism
MLH1
MLH1 protein
MSH2
MSH2 protein
MSH6
MSH6 protein
Mutants
Mutation
MutL Protein Homolog 1 - genetics
MutL Protein Homolog 1 - metabolism
Neurology
Patients
PD-L1 protein
PMS2
Prognosis
Proteins
Survival Rate
Tumors
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Summary:The diagnostic role of Isocitrate Dehydrogenase (IDH) mutation status in adult lower grade astrocytomas was first formally presented within the WHO Classification of Tumours of the Central Nervous System (2016). IDH-mutant astrocytomas are not as common as IDH-wildtype astrocytomas but are of better prognosis. Our previous study provided an evident that IDH-mutant lower grade astrocytomas is not a homogeneous group and could be further stratified by PDGFRA amplification, CDK4 amplification and CDKN2A deletion. In this study, we detected the expressions of DNA mismatch repair (MMR) proteins (PMS2, MLH1, MSH2, MSH6) and PD-L1 by immunohistochemistry in 147 IDH-mutant lower grade astrocytomas and explored their clinical relevance. The loss of was identified in 28.6%, 1.4%, 8.8% and 13.6%, respectively. PD-L1 expression was detected in 1.4% of this cohort. Survival analysis revealed that loss of PMS2 was correlated with shorter OS (p 
ISSN:0303-8467
1872-6968
DOI:10.1016/j.clineuro.2021.106882