Analysis of Histomorphological/molecular Association and Immune Checkpoint Regulators in Epithelioid Glioblastoma and Pleomorphic Xanthoastrocytoma: Are These Tumors Potential Candidate for Immune Checkpoint Blockade

Abstract IntroductionEpithelioid 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 methodsTwenty 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).ResultsPXA 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%). ConclusionThis 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.