Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 23:13:8755-8765.
doi: 10.2147/CMAR.S336213. eCollection 2021.

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

Zixi Yang  1 , Feng Ling  1 , Sibei Ruan  1 , Jiajia Hu  2 , Mingxi Tang  1 , Xingwang Sun  1 , Wenbo Long  1
Affiliations

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

Zixi Yang et al. Cancer Manag Res. .

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 diagnosis, 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.

Keywords: biomarker; correlation analysis; genetic alteration; human glioma; survival rate.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Prognostic values of patient age, histological grade, MGMT promoter methylation, IDH mutation, TERT promoter mutation, 1p/19q codeletion, and Ki-67 and p53 expressions by Kaplan–Meier Estimates of Overall Survival in 103 gliomas.
Figure 2
Figure 2
Kaplan–Meier estimates of overall survival in the glioma molecular groups.
See this image and copyright information in PMC

References

    1. Labreche K, Kinnersley B, Berzero G, et al. Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci. Acta Neuropathol. 2018;135(5):743–755. - PMC - PubMed
    1. Pienkowski T, Kowalczyk T, Kretowski A, Ciborowski M. A review of gliomas-related proteins. Characteristics of potential biomarkers. Am J Cancer Res. 2021;11(7):3425–3444. - PMC - PubMed
    1. van den Bent MJ. Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician’s perspective. Acta Neuropathol. 2010;120(3):297–304. - PMC - PubMed
    1. Chen WJ, He DS, Tang RX, Ren FH, Chen G. Ki-67 is a valuable prognostic factor in gliomas: evidence from a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2015;16(2):411–420. - PubMed
    1. Jin Y, Xiao W, Song T, Feng G, Dai Z. Expression and prognostic significance of p53 in glioma patients: a meta-analysis. Neurochem Res. 2016;41(7):1723–1731. - PubMed