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Research Article
Vaishali Suri
All India Institute of Medical Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6485-8194
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Introduction
Epithelioid glioblastoma (eGB) was adopted as a provisional entity in the 2016 WHO classification of central nervous tumors. Accurate diagnosis of eGBs and pleomorphic xanthoastrocytoma (PXA) is sometimes challenging owing to overlapping histological and genetic features. There are limited reports on immune profile of these tumors.
Materials and methods
Twenty one PXA’s [15 PXA, 6 Anaplastic-PXA (A-PXA) and 14 eGB’s were assessed for histopathological and molecular association and their immune profile was compared to primary (1°) GBs (n-18).
Results
PXA cases showed extensive whereas variable positivity for epithelial and glial markers was seen in A-PXAs and eGBs. All cases showed retained nuclear ATRX and INI-1. H3K27M or IDH mutation was seen in none. P53 mutation was more common in eGB’s (57%) and A-PXA (33.33%) as compared to PXA (13.33%). None of the 1° GB’s harbored BRAF V600E, which was observed in 57% PXA and 50% eGBs with 100% concordance between immunohistochemistry and sequencing. EGFR amplification was observed in 14% eGB’s and 66% of 1° GB’s. PDL1 and CTLA-4 expression was higher in eGB’s (71.4% & 57.1%), A-PXA (66.6% &100%) and PXA (60% & 66.7%) as compared to 1° GB’s (38.8% & 16.7%). T cell infiltration was also observed in majority of eGB’s and PXA (90-100%) cases in contrast to 1°GB’s (66%).
Conclusion
This is the first comprehensive analysis highlighting homogenous molecular profile and immune microenvironment of eGB and PXA, suggesting that they are closely related. Upregulation of PD-L1, CTLA4 and increased TIL’s in these tumors suggests potential candidature for immunotherapy.
Keywords
Epithelioid glioblastoma, Pleomorphic xanthoastrocytoma, BRAF V600E, PDL1, CTLA4, CD3, CD8
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This is a preprint. It has not completed peer review.
Research Article
Vaishali Suri
All India Institute of Medical Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6485-8194
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 15 Mar, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Introduction
Epithelioid glioblastoma (eGB) was adopted as a provisional entity in the 2016 WHO classification of central nervous tumors. Accurate diagnosis of eGBs and pleomorphic xanthoastrocytoma (PXA) is sometimes challenging owing to overlapping histological and genetic features. There are limited reports on immune profile of these tumors.
Materials and methods
Twenty one PXA’s [15 PXA, 6 Anaplastic-PXA (A-PXA) and 14 eGB’s were assessed for histopathological and molecular association and their immune profile was compared to primary (1°) GBs (n-18).
Results
PXA cases showed extensive whereas variable positivity for epithelial and glial markers was seen in A-PXAs and eGBs. All cases showed retained nuclear ATRX and INI-1. H3K27M or IDH mutation was seen in none. P53 mutation was more common in eGB’s (57%) and A-PXA (33.33%) as compared to PXA (13.33%). None of the 1° GB’s harbored BRAF V600E, which was observed in 57% PXA and 50% eGBs with 100% concordance between immunohistochemistry and sequencing. EGFR amplification was observed in 14% eGB’s and 66% of 1° GB’s. PDL1 and CTLA-4 expression was higher in eGB’s (71.4% & 57.1%), A-PXA (66.6% &100%) and PXA (60% & 66.7%) as compared to 1° GB’s (38.8% & 16.7%). T cell infiltration was also observed in majority of eGB’s and PXA (90-100%) cases in contrast to 1°GB’s (66%).
Conclusion
This is the first comprehensive analysis highlighting homogenous molecular profile and immune microenvironment of eGB and PXA, suggesting that they are closely related. Upregulation of PD-L1, CTLA4 and increased TIL’s in these tumors suggests potential candidature for immunotherapy.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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