Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas

// Jinquan Cai 1, 7, * , Ping Zhu 4, * , Chuanbao Zhang 2, 3, 7, * , Qingbin Li 1, 7 , Zhiliang Wang 2, 3, 7 , Guanzhang Li 2, 3, 7 , Guangzhi Wang 1, 7 , Pei Yang 2, 3, 7 , Jianlong Li 2, 7 , Bo Han 2, 7 , Chuanlu Jiang 1, 7 , Ying Sun 1, 7 , Tao Jiang 2, 3, 5, 6, 7 1 Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China 2 Beijing Neurosurgical Institute, Capital Medical University, Beijing, China 3 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 4 Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 5 Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, China 6 China National Clinical Research Center for Neurological Diseases, Beijing, China 7 Chinese Glioma Cooperative Group (CGCG), Beijing, China * These authors contributed equally to the work Correspondence to: Chuanlu Jiang, e-mail: jcl6688@163.com Tao Jiang, e-mail: taojiang1964@163.com Ying Sun, e-mail: sunying701211@163.com Keywords: IDH1-R132H, ATRX loss, glioma, progression, evolution Received: October 25, 2015      Accepted: January 29, 2016      Published: February 24, 2016 ABSTRACT Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. A small residual population of cells always escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence or progression. IDH mutation (isocitrate dehydrogenase) and ATRX (alpha-thalassemia/mental retardation, X-linked) loss/mutation occur in association and may represent early genetic alterations in the development of gliomas. However, their prognostic value in the evolution of gliomas still needs further investigation. Two hundreds and eleven serial sampling of gliomas were included in our study. We used immunohistochemistry (IHC) to detect IDH1-R132H mutation and ATRX status and showed that the IDH1-R132H and (or) ATRX status could be necessary to provide the basic molecular information for the “integrated diagnosis” of gliomas. We illustrated an evaluation formula for the evolution of gliomas by IDH1-R132H combined with ATRX immunohistochemistry and identified the association of IDH1-R132H/ATRX loss accompanied by longer progression time interval of patients with gliomas. Furthermore, we observed that most recurrences had a consistent IDH1 and ATRX status with their matched primary tumors and demonstrated the progressive pattern of grade II astrocytoma/oligodendroglial tumors and anaplastic oligoastrocytoma with or without IDH1-R132H. Identification of IDH1-R132H and ATRX loss status in the primary-recurrent gliomas may aid in treatment strategy selection, therapeutic trial design, and clinical prognosis evaluation.