PATH-58. MISMATCH REPAIR DEFICIENCY (MMRd) IN GLIOMA PATIENTS (PTS): FREQUENCY AND CORRELATION WITH CLINICAL, HISTOLOGICAL AND MOLECULAR CHARACTERISTICS. (5th November 2018)

• Record Type: Journal Article
• Authors: Lombardi, Giuseppe; Caccese, Mario; Simonelli, Matteo; Fassan, Matteo; Persico, Pasquale; Lorenzi, Elena; Bertorelle, Roberta; Paola Gardiman, Marina; Bellu, Luisa; Pambuku, Ardi; Santoro, Armando; Zagonel, Vittorina
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi171
• Page End: vi171
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.712
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Immunecheckpoint inhibitors (ICI) represent a new approach in oncology. The DNA MMRd would seem to be a predictor of ICI efficacy. We analyzed MMRd frequency in glioma PTS and its correlation with clinical, histological and molecular characteristics. METHODS: From July 2017 to May 2018, we prospectively analyzed glioma PTS for the presence of MMRd by immunohistochemistry (IHC): MSH2, MSH6, PMS2, MLH1. Clinical, histological and molecular characteristics were recorded. Chi-square test was used for analyzing their correlations with MMRd. RESULT: 167 PTS enrolled: 78% glioblastoma (GBM), 14% anaplastic astrocytoma (AA), 1% ependymoma, 2% anaplastic oligodendroglioma (OD) and 5%LGG. The analyses were assessed on samples of first (82%) and second surgery (18%). 134 PTS analyzed for IDH status: 99 IDH wt; 117 for MGMT: 68 methylated. 27PTS (16%) showed MMRd by IHC (MSH2 in 48%, MSH6 in 55.6%, PMS2 in 18.5% and MLH1 in 14.8%): 33% of AA, 14% of GBM, 33% of OD and 0% of LGG (p=0.2). MMRd was found in 13% and 32% on first and second surgery samples (p=0.03). PD-L1 expression analysis was performed in 60 cases: no expression in 58%, ≥1%and<50% in 38%; ≥50% in 10%. MMRd was not correlated with PD-L1 expression (p=0.3). MMRd was found in 10% and 29% of IDHwt and IDHmut gliomas(p=0.008); MMRd was showed in 10% and 21% of PTS with unmet and metMGMT(p=0.1). Among MMRd tumors, 7 were also investigated by molecular analysis (PCR) of mononucleotide markers: in only 1PT (14%) was confirmed MMRd in agreement with IHC analysis (p=0.1.). CONCLUSIONS: We showed a small group of glioma PTS have MMRd by IHC, expecially at second surgery. Correlation was observed between IHC MMRd and IDH mutational status. No association was demonstrated between IHC MMRd and histology, MGMT status, PD-L1 expression or molecular analysis of MMRd. A prospective study analyzing ICI efficacy in MMRd PTS should be warranted.