Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study.
Int J Mol Sci
; 21(18)2020 Sep 14.
Article
in En
| MEDLINE
| ID: mdl-32937743
ABSTRACT
BACKGROUND:
DNA mismatch repair (MMR) is a system for repairing errors in DNA replication. Cancer cells with MMR deficiency can have immunohistochemical loss of MMR protein expression leading to a hypermutable phenotype that may correlate with anti-PD1 efficacy. Scant data exist about immunohistochemical loss of MMR protein expression in high-grade gliomas (HGG). MATERIALS ANDMETHODS:
We performed a large multicenter retrospective study to investigate the frequency and the prognostic role of immunohistochemical loss of MMR protein expression in HGG patients; we nevertheless evaluated the association between this status and clinical or molecular characteristics. Immunohistochemical loss of MMR protein expression was recorded as partial or complete loss of at least 1 MMR protein.RESULTS:
We analyzed the expression of MMR proteins in tumor tissue of 355 consecutive patients. Partial and complete immunohistochemical loss of MMR proteins was found in 43/355 samples (12.1%) and among these, 15 cases (4.2%) showed a complete loss of at the least one MMR protein. Alteration of MSH2 expression was found in 55.8%, MSH6 in 46.5%, PMS2 in 34.9%, and MLH1 in 30.2%. Alteration of MMR protein expression was statistically more frequent in anaplastic gliomas, in recurrent disease, in patients treated with temozolomide, and in IDH-mut gliomas. Immunohistochemical loss of MMR proteins was not associated with survival, adjusting for clinically relevant confounders.CONCLUSIONS:
MMR protein expression status did not affect survival in HGG patients. We identified clinical and molecular characteristics correlating with immunohistochemical loss of MMR proteins expression. A large study should be performed to analyze its predictive role of immune checkpoint inhibitor efficacy in these subgroups of patients.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA-Binding Proteins
/
DNA Mismatch Repair
/
Glioma
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Int J Mol Sci
Year:
2020
Document type:
Article
Affiliation country:
Italy
Publication country:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND