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Oligodendrogliomas in pediatric and teenage patients only rarely exhibit molecular markers and patients have excellent survivals

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Abstract

Although oligodendrogliomas appear histologically similar in adult and pediatric patients, the latter have only been rarely studied and most of those studies did not have long follow-up. We examined 55 oligodendroglial tumors from pediatric and teenage patients for their biomarkers with formalin-fixed paraffin-embedded tissues and studied their survival status. None of the tumors harbored 1p/19q codeletion or IDH mutation. Mutations in TERTp (4%), BRAF (11%), FGFR1 (3%) and H3F3A (5%), fusions of BRAF (8%) and FGFR1 (8%) were found sparingly and almost all in a mutually exclusive manner. Molecular events were exclusively found in tumors with classic oligodendroglial histology. Survival analysis showed remarkably excellent prognosis compared to the adult counterparts. 5-year overall survival was 95% in our cohort with median follow-up of 8.1 years and in nine patients with follow-up more than 10 years, the 10-year overall survival was 100%. The 5-year and 10-year progression-free survivals of our cohort were 89 and 77%, respectively. FGFR1 fusion seemed to confer a poor prognosis in pediatric oligodendrogliomas. Patients receiving adjuvant chemotherapy (p = 0.046) or harboring Grade II histology (p < 0.001) had longer interval to recurrence. Our study demonstrated the distinct indolent clinical course of pediatric and teenage oligodendrogliomas compared to the adult tumors. Molecular markers commonly seen in adult oligodendrogliomas and other pediatric low-grade gliomas were only rarely seen. Since there is no clinical or molecular evidence suggesting that pediatric “oligodendrogliomas” are the same as adult oligodendrogliomas albeit histologic similarity, a case can be made for their separation from adult oligodendrogliomas in the next WHO classification.

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Acknowledgements

This study was supported by Health and Medical Research Fund of Hong Kong (Grant No. 02133146), S.K. Yee Medical Foundation (2151229), and 973 Program (Grant No. 2015CB755500). We would like to give our great thanks to Professor Cynthia Hawkins for providing us the NanoString Panel in this study.

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  1. Yan-Xi Li and Aibaidula Abudumijiti have contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China

    Yan-Xi Li, Kay Ka-Wai Li, Nellie Yuk-Fei Chung, Ryan Rui Yang, Aden Ka-yin Chan & Ho-Keung Ng

  2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

    Yan-Xi Li, Abudumijiti Aibaidula, Zhifeng Shi, Ying Mao, Jinsong Wu & Liangfu Zhou

  3. Department of Neuropathology, Huashan Hospital, Fudan University, Shanghai, China

    Hong Chen

  4. Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China

    Yan-Xi Li, Kay Ka-Wai Li, Nellie Yuk-Fei Chung, Ryan Rui Yang & Ho-Keung Ng

  5. Neurosurgery Division, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China

    Danny Tat-Ming Chan & Wai Sang Poon

  6. Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong, China

    Ka Lok Ryan Lee

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  1. Yan-Xi Li
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Correspondence to Jinsong Wu or Aden Ka-yin Chan.

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Supplementary Figure 1. Correlations between clinicopathological factors and molecular variables. a

All biomarkers examined in our study were exclusively detected in tumors with classic oligodendroglial histology (p=0.002). b WHO grade II was associated with younger age of the patients at the time of diagnosis (p<0.001). c TERTp mutation was exclusively detected in anaplastic oligodendroglial tumors (p=0.005). d Among the six patients who experienced tumor recurrence, five cases occurred in the temporal lobe (p=0.08). −ve, negative; +ve, positive; O, oligodendroglioma, NOS; OA, oligoastrocytoma, NOS. Supplementary Figure 2. Kaplan-Meier survival analysis. a Grade III histology had a significantly shorter overall survival than those with grade II histology (p&#x003C;0.001). b Patients of age above 15 years showed trend of shorter overall survival (p=0.062). c Temporal lobe tumors exhibited a trend of shorter progression-free survival as compared to tumors of other locations (p=0.15). d-e No patient death or tumor recurrence was observed among these BRAF aberrated pediatric oligodendroglial tumors. f Among temporal lobe tumors, negative CD34 expression was associated with shorter progression-free survival (p=0.039). OS, overall survival; PFS, progression-free survival; -ve, negative; +ve, positive. Supplementary Figure 3. Representative photomicrographs of cases in our study. Oligodendroglioma – cases 20, 42, 49, and 52; Oligoastrocytoma – case 37; Anaplastic oligodendroglioma – case 6. Regrettably, the radiologic images of these cases were already archived by the hospitals. Supplementary Figure 4. Paired MRI (T1) images and H&E photos of cases in this study. (PPTX 41249 KB)

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Li, YX., Aibaidula, A., Shi, Z. et al. Oligodendrogliomas in pediatric and teenage patients only rarely exhibit molecular markers and patients have excellent survivals. J Neurooncol 139, 307–322 (2018). https://doi.org/10.1007/s11060-018-2890-9

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