Research Papers: Pathology:

Combination genetic signature stratifies lower-grade gliomas better than histological grade

Aden Ka-Yin Chan, Yu Yao, Zhenyu Zhang, Zhifeng Shi, Liang Chen, Nellie Yuk-Fei Chung, Joseph Shu-Ming Liu, Kay Ka-Wai Li, Danny Tat-Ming Chan, Wai Sang Poon, Liangfu Zhou and Ho-Keung Ng _

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Oncotarget. 2015; 6:20885-20901. https://doi.org/10.18632/oncotarget.4928

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Aden Ka-Yin Chan1,2,*, Yu Yao4,*, Zhenyu Zhang4, Zhifeng Shi4, Liang Chen4, Nellie Yuk-Fei Chung1,2, Joseph Shu-Ming Liu1,2, Kay Ka-Wai Li1,2, Danny Tat-Ming Chan3, Wai Sang Poon3, Ying Wang5, Liangfu Zhou4, Ho-Keung Ng1,2

1Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Shatin, Hong Kong

2Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China

3Neurosurgery Division, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong Kong

4Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

5Department of Neuropathology, Huashan Hospital, Fudan University, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Ho-Keung Ng, e-mail: [email protected]

Liangfu Zhou, e-mail: [email protected]

Keywords: Pathology Section, glioma, IDH1/2, 1p/19q, TERT, EGFR

Received: April 17, 2015     Accepted: July 30, 2015     Published: August 11, 2015


We studied if combination genetic signature potentially stratifies lower-grade gliomas better than histology by investigating 214 lower-grade gliomas for IDH1/2 and TERTp mutations, 1p/19q codeletion and EGFR amplification as to their impact on prognostication. Prognostic association of grading was independent of other prognostic variables including age, histological type, IDH1/2, 1p/19q and TERTp status. No single marker, including IDH1/2, superseded grading in prognostication, indicating grading was still a very important tool. Prognosis was most favorable in 31.7% of patients with IDH1/2 mutation and either 1p/19q codeletion or TERTp mutation (IDHmut-OT), intermediate in 45.8% of patients with IDH1/2 mutation only (IDHmut) and 16.9% of patients without any of the alterations (IDHwt), and poorest in 5.6% of patients with wild-type IDH1/2 and either TERTp mutation or EGFR amplification (IDHwt-ET). Our results suggested not all IDH1/2 wild-type lower-grade gliomas are aggressive and additional biomarkers are required to identify glioblastoma-equivalent tumors. Multivariate analysis revealed independent prognostic values of grading and genetic signature. Grade II IDHwt-ET gliomas exhibited shorter survival than IDH1/2 mutated grade III gliomas, suggesting combination genetic signature potentially superseded grading in prognostication. In summary, biomarker-based stratification is useful in the diagnosis and prognostication of lower-grade gliomas, and should be used together with grading.

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