Clinical and prognostic implications of 1p/19q, idh, braf, mgmt promoter, and tert promoter alterations, and expression of ki-67 and p53 in human gliomas

Abstract

Background and Objective: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diag-nosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood. Methods: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II–IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry. Results: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis. Conclusion: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.