title: Combination genetic signature stratifies lower-grade gliomas better than histological grade.
abstract: 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 No single marker, including IDH1/2, superseded grading in prognostication, indicating grading was still a very important tool.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exhibited shorter survival than IDH1/2 mutated grade III gliomas, suggesting combination genetic signature potentially superseded grading in prognostication.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.
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Aden Ka-Yin
authors.initials: AK
authors.lastname: Chan
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Nellie Yuk-Fei
authors.initials: NY
authors.lastname: Chung
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Joseph Shu-Ming
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Kay Ka-Wai
authors.initials: KK
authors.lastname: Li
authors.affiliation: Neurosurgery Division, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Danny Tat-Ming
authors.initials: DT
authors.lastname: Chan
authors.affiliation: Neurosurgery Division, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Wai Sang
authors.initials: WS
authors.lastname: Poon
authors.affiliation: Department of Neuropathology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002872:Chromosome Deletion; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D060787:Neoplasm Grading; D011379:Prognosis; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C509186:TERT protein, human; D019098:Telomerase
keywords: 1p/19q; EGFR; IDH1/2; Pathology Section; TERT; glioma