Microsatellite instability in glioblastoma: is it really relevant in tumor prognosis?

Abstract

AIM: To evaluate the frequency and prognostic significance of microsatellite instability (MSI) in patients with glioblastoma (GBM), an immunohistochemical analysis of mismatch repair (MMR) proteins was performed. MATERIAL and METHODS: A total of 71 patients with GBM who underwent surgery between 2011 and 2019, were included in the study. MMR protein expression was examined using immunohistochemistical analysis of tumor tissue samples; the association between the MMR status and clinicopathological findings was evaluated. RESULTS: Immunohistochemical analysis revealed expressions of MLH1, MSH2, MSH6, and PMS2 proteins in 67 (94.4%), 65 (91.5%), 67 (94.4%), and 64 (90.1%) patients, respectively. Among the 71 patients, 64 (90.1%) expressing all MMR proteins were considered microsatellite stable (MSS), and 7 (9.9%) patients showing loss of at least one of the MMR proteins were considered to show MSI. Tumor recurrence was noted in 25 (39.1%) patients in the MSS GBM group, and 4 (57.1%) patients in the MSI GBM group (p=0.433). The overall median survival was 30.65 ± 5.1 and 10.71 ± 5.2 months in the MSS GBM and MSI GBM groups, respectively (p=0.059). CONCLUSION: The results of this study showed no significant relationships between MMR protein expression and recurrence rates or overall survival in patients with GBM.

EZH2 is a potential prognostic predictor of glioma

“…DNA MMR deficiency causes genomic instability and results in the accumulation of numerous mutations in microsatellite sequences that lead to MSI. Furthermore, MSI has been investigated as a molecular mechanism that is indicative of the prognosis and treatment response in glioma 26 . Here, we used Spearman's correlation analysis to evaluate the relationship between EZH2 expression and glioma MSI; however, there was no relevance between EZH2 expression and MSI in GBM.…”

How Should We Test for Lynch Syndrome? A Review of Current Guidelines and Future Strategies

“…However, one interesting aspect is that the frequency of MMR deficiency in CNS tumours may depend on the detection method used. For example, Bonneville et al [208] found that only 0.3% (3/909; 95% CI: 0.1-1.0%) of glioblastoma were MMR deficient using MSI analysis, but Tepeoglu et al [233] found, in contrast, that 9.9% (7/71; 95% CI: 4.1-19.3%) were MMR deficient using IHC. Studies of glioblastoma diagnosed in patients with constitutional mismatch repair deficiency (CMMRD), a paediatric cancer predisposition syndrome caused by germline pathogenic variants in both alleles of an MMR gene [238], have previously shown that increased MSI could not be detected despite loss of MMR protein expression in the tumour or detection of MSI-H in synchronous adenocarcinomas [239][240][241].…”

Therapeutic and Diagnostic Potential of Exosomes as Drug Delivery Systems in Brain Cancer

“…Moreover, unraveling the employment of different cargo molecules, in case their chemistry permits the encapsulation into exosomes, such as drugs, miRNAs with a tumor-suppressing nature, or anti-miRNAs acting as expression suppressors of oncogenic miRNAs, would also be of great interest. In order to plan an individualized therapy strategy and provide more accurate therapeutic assays, it is crucial to elucidate the underlying molecular mechanisms that induce oncogenesis and genomic/microsatellite instability in different brain cancer forms, e.g., GBM, with the aim to intervene in the suppression of the generated phenotype [ 261 , 262 , 263 ].…”