P11.22.A Prognostic and predictive relevance of immunohistochemically determined p53 mutation in glioblastoma

Abstract

Abstract Background It can be expected that molecular biomarkers will increasingly affect clinical decisions and lead to the development of more personalized therapies in glioblastoma (GBM) in the future. In several other tumor entities TP53 gene mutation or p53 immunoreactivity (IR) serve as a prognostic marker, significantly affecting overall survival (OS) and progression-free survival (PFS). Such an association has not yet sufficiently been demonstrated in GBM. However, there are known prognostic markers in GBM, notably MGMT promotor methylation (mMGMT) which also serves as an important predictive marker leading to a better response to temozolomide chemotherapy. Our aim was to evaluate retrospectively if p53 mutation determined via immunohistochemistry (IHC) could act as a prognostic or predictive marker in GBM. Material and Methods Tumor samples of 195 treatment-naïve patients with IDHwt GBM that had been stained with the p53 antibody DO-7 were subdivided into 2 different groups by p53 IHC. Samples were considered as p53mut when strong p53 IR was detected in ≥10% of all tumor cells and as p53wt when in <10%. Treatment, further molecular and survival data were gathered retrospectively for all patients. Statistical analyses were performed with SPSS. Results The frequency of p53mut was 36.4% (71/195). p53mut tumors showed a significantly higher IR with Ki-67 proliferation marker (p=0.005) and p53wt seemed to be associated with multifocal primary tumor localization, though not statistically significant (p=0.107). There was no significant difference between p53wt and p53mut regarding gender, age, extent of resection, adjuvant therapy, occurrence of seizures, mMGMT or ATRX loss. The p53 status was not associated with OS or PFS. Factors that univariately led to significantly longer OS and PFS were younger age, unilateral or unifocal primary tumor localization, gross-total resection, higher Karnofsky Performance Status (KPS), mMGMT and adjuvant treatment via Stupp regimen instead of radiotherapy alone, the latter being significantly better than best supportive care. In multivariate survival analyses only age <65 years, the Stupp regimen more than radiotherapy alone and KPS ≥80% significantly prolonged both OS and PFS. Unifocal primary tumor localization led to longer OS and mMGMT led to longer PFS independently. The p53 status did not significantly affect the response to different adjuvant therapy regimens neither concerning OS nor PFS. Conclusion Based on our study, p53 IR has no prognostic or predictive significance in IDHwt GBM. There have been previous studies with similar and others with contradicting results. Remarkable is the discordance of the used IR thresholds between different studies. Further studies should aim to revalidate the staining threshold and improve the concordance between TP53 gene sequencing and p53 IHC in IDHwt GBM.