Oncotarget

Research Papers: Pathology:

Not all 1p/19q non-codeleted oligodendroglial tumors are astrocytic

Yan-Xi Li _, Zhifeng Shi, Abudumijiti Aibaidula, Hong Chen, Qisheng Tang, Kay Ka-Wai Li, Nellie Yuk-Fei Chung, Danny Tat-Ming Chan, Wai Sang Poon, Ying Mao, Jinsong Wu, Liangfu Zhou, Aden Ka-yin Chan and Ho-Keung Ng

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Oncotarget. 2016; 7:64615-64630. https://doi.org/10.18632/oncotarget.11378

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Abstract

Yan-Xi Li1,2,4,*, Zhifeng Shi4,*, Abudumijiti Aibaidula4, Hong Chen5, Qisheng Tang4, Kay Ka-Wai Li1,2, Nellie Yuk-Fei Chung1,2, Danny Tat-Ming Chan3, Wai Sang Poon3, Ying Mao4, Jinsong Wu4, Liangfu Zhou4, Aden Ka-yin Chan1,2 and Ho-Keung Ng1,2

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

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

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

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

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

* These authors have contributed equally to this work

Correspondence to:

Aden Ka-yin Chan, email:

Liangfu Zhou , email:

Keywords: oligodendroglial tumors, intact 1p/19q, TERT, IDH, Pathology Section

Received: April 19, 2016 Accepted: August 12, 2016 Published: August 18, 2016

Abstract

Although 1p/19q codeletion is the genetic hallmark defining oligodendrogliomas, approximately 30-40% of oligodendroglial tumors have intact 1p/19q in the literature and they demonstrate a worse prognosis. This group of 1p/19q intact oligodendroglial tumors is frequently suggested to be astrocytic in nature with TP53 and ATRX mutations but actually remains under-investigated. In the present study, we provided evidence that not all 1p/19q intact oligodendroglial tumors are astrocytic through histologic and molecular approaches. We examined 1p/19q status by FISH in a large cohort of 337 oligodendroglial tumors and identified 39.8% lacking 1p/19q codeletion which was independently associated with poor prognosis. Among this 1p/19q intact oligodendroglial tumor cohort, 58 cases demonstrated classic oligodendroglial histology which showed older patient age, better prognosis, association with grade III histology, PDGFRA expression, TERTp mutation, as well as frequent IDH mutation. More than half of the 1p/19q intact oligodendroglial tumors showed lack of astrocytic defining markers, p53 expression and ATRX loss. TP53 mutational analysis was additionally conducted in 45 cases of the 1p/19q intact oligodendroglial tumors. Wild-type TP53 was detected in 71.1% of cases which was associated with classic oligodendroglial histology. Importantly, IDH and TERTp co-occurred in 75% of 1p/19q intact, TP53 wild-type oligodendrogliomas, highlighting the potential of the co-mutations in assisting diagnosis of oligodendrogliomas in tumors with clear cell morphology and non-codeleted 1p/19q status. In summary, our study demonstrated that not all 1p/19q intact oligodendroglial tumors are astrocytic and co-evaluation of IDH and TERTp mutation could potentially serve as an adjunct for diagnosing 1p/19q intact oligodendrogliomas.


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