Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide

Autor(es)

Gomes, Isabella ^[1] ; Moreno, Daniel Antunes ^[1] ; dos Reis, Mariana Bisarro ^[1] ; da Silva, Luciane Sussuchi ^[1] ; Leal, Leticia Ferro ^{[2, 1]} ; Goncalves, Gisele Melo ^[3] ; Pereira, Caio Augusto ^[3] ; Oliveira, Marco Antonio ^[4] ; Matsushita, Marcus de Medeiros ^[5] ; Reis, Rui Manuel ^{[6, 7, 1]}

Afiliação do(s) autor(es)

^[1] Barretos Canc Hosp BCH, Mol Oncol Res Ctr, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil

^[2] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, Barretos - Brazil

^[3] BCH, Dept Med Oncol, Barretos, SP - Brazil

^[4] BCH, Nucleus Epidemiol & Stat, Barretos, SP - Brazil

^[5] BCH, Pathol Dept, Barretos, SP - Brazil

^[6] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[7] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEURO-ONCOLOGY; v. 151, n. 2 JAN 2021.
• Citações Web of Science: 0

Resumo

Introduction Glioblastoma (GBM) is the deadliest primary brain tumor. The standard treatment consists of surgery, radiotherapy, and temozolomide (TMZ). TMZ response is heterogeneous, and MGMT promoter (MGMTp) methylation has been the major predictive biomarker. We aimed to describe the clinical and molecular data of GBMs treated with TMZ, compare MGMT methylation with MGMT expression, and further associate with patient's outcome. Methods We evaluate 112 FFPE adult GBM cases. IDH1 and ATRX expression was analyzed by immunohistochemistry, hotspot TERT promoter (TERTp) mutations were evaluated by Sanger or pyrosequencing, and MGMTp methylation was assessed by pyrosequencing and MGMT mRNA expression using the nCounter (R) Vantage 3D (TM) DNA damage and repair panel. Results Of the 112 GBMs, 96 were IDH1(WT), and 16 were IDH1(MUT). Positive ATRX expression was found in 91.6% (88/96) of IDHWT and 43.7% (7/16) of IDHMUT. TERTp mutations were detected in 70.4% (50/71) of IDHWT. MGMTp methylation was found in 55.5% (35/63) of IDHWT and 84.6% (11/13) of IDHMUT, and as expected, MGMTp methylation was significantly associated with a better response to TMZ. MGMT expression was inversely correlated with MGMTp methylation levels (- 0.506, p < 0.0001), and MGMT low expression were significantly associated with better patient survival. It was also observed that integrating MGMTp methylation and expression, significantly improved the prognostication value. Conclusions MGMT mRNA levels evaluated by digital expression were associated with the outcome of TMZ-treated GBM patients. The combination of MGMT methylation and mRNA expression may provide a more accurate prediction of TMZ response in GBM patients. (AU)

• Processo FAPESP: 18/10511-6 - Identificação de biomarcadores preditivos da resposta ao tratamento com temozolomida no glioblastoma
• Beneficiário: Isabella Gomes
• Modalidade de apoio: Bolsas no Brasil - Mestrado