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
Comparative Study
. 2015 Oct 6;6(30):30232-8.
doi: 10.18632/oncotarget.4920.

IDH1/2 mutation status combined with Ki-67 labeling index defines distinct prognostic groups in glioma

Ailiang Zeng  1 , Qi Hu  1 , Yanwei Liu  2 , Zheng Wang  2 , Xiaoming Cui  1 , Rui Li  1 , Wei Yan  1 , Yongping You  1
Affiliations
Comparative Study

IDH1/2 mutation status combined with Ki-67 labeling index defines distinct prognostic groups in glioma

Ailiang Zeng et al. Oncotarget. .

Abstract

The current World Health Organization (WHO) classification of human gliomas is mainly based on morphology. However, it has limitations in prognostic prediction. We examined whether combining isocitrate dehydrogenase (IDH) 1/2 mutation status with the Ki-67 labeling index would improve the definition of prognostically distinct entities. We investigated the correlation of Ki-67 expression with IDH1/2 mutation status and their impact on clinical outcome in 703 gliomas. Low Ki-67 expression closely overlapped with IDH1/2 mutation in our cohort (P < 0.0001). Patients with IDH1/2 mutation survived significantly longer than patients with wild-type IDH1/2 did (P < 0.0001); higher Ki-67 expression was associated with shorter progression-free survival and overall survival (OS) (P < 0.0001). IDH1/2 combined with Ki-67 was used to re-classify glioma patients into five groups. IDH1/2 mutant patients with low and moderate Ki-67 expression (Group1) had the best prognosis, whereas patients with wild-type IDH1/2 and high Ki-67 expression (Group5) had the worst prognosis (Median OS = 1527 vs. 355 days, P < 0.0001). To summarize, our new classification model distinguishes biologically distinct subgroups and provides prognostic information regardless of the conventional WHO grade. Classification based on IDH1/2 mutation status and Ki-67 expression level could be more convenient for clinical application and guide personalized treatment in malignant gliomas.

Keywords: IDH1/2 mutation; Ki-67 labeling index; glioma; molecular classification; prognosis.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

None of the authors has any conflict of interest to disclose.

Figures

Figure 1
Figure 1. Progression free survival and overall survival among all 703 gliomas
A. Progression free survival and overall survival among all 703 gliomas stratified by IDH1/2 mutant status; B. Progression free survival and overall survival among all 703 gliomas stratified by relative Ki-67 expression level.
Figure 2
Figure 2. Distribution of low, moderate and high Ki-67 expression among IDH1/2 mut and IDH1/2 wt group
A. Ki-67 expression was determined in IDH1/2 mut group; B. Ki-67 expression was determined in IDH1/2 wt group.
Figure 3
Figure 3. Kaplan-Meier estimates of survival for all 703 gliomas
A. Progression free survival and overall survival among IDH1/2 mutant tumors stratified by relative Ki-67 expression level; B. Progression free survival and overall survival among IDH1/2 wild type tumors stratified by relative Ki-67 expression level.
Figure 4
Figure 4. Model for classification of gliomas based on molecular markers
IDH1/2 mutant tumors with low and moderate Ki-67 expression was termed as Group 1, IDH1/2 mutant tumors with high Ki-67 expression as Group 2, IDH1/2 wt tumors with low Ki-67 expression as Group 3, IDH wt tumors with moderate Ki-67 expression as Group 4, and IDH wt tumors with high Ki-67 expression was defined as Group 5.
Figure 5
Figure 5. Progression free survival and overall survival among the new five groups
A. Progression free survival among the new five groups stratified by combined IDH mutation and Ki-67 expression status; B. overall survival among the new five groups stratified by combined IDH mutation and Ki-67 expression status.
See this image and copyright information in PMC

References

    1. Kannan K, Inagaki A, Silber J, Gorovets D, Zhang J, Kastenhuber ER, Heguy A, Petrini JH, Chan TA, Huse JT. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget. 2012;3:1194–1203. - PMC - PubMed
    1. Wen PY, Kesari S. Malignant gliomas in adults. The New England journal of medicine. 2008;359:492–507. - PubMed
    1. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, et al. IDH1 and IDH2 mutations in gliomas. The New England journal of medicine. 2009;360:765–773. - PMC - PubMed
    1. Olar A, Wani KM, Alfaro-Munoz KD, Heathcock LE, van Thuijl HF, Gilbert MR, Armstrong TS, Sulman EP, Cahill DP, Vera-Bolanos E, Yuan Y, Reijneveld JC, Ylstra B, Wesseling P, Aldape KD. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol. 2015;129:585–596. - PMC - PubMed
    1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta neuropathologica. 2007;114:97–109. - PMC - PubMed

Publication types

MeSH terms