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.
Highlights
Diffuse gliomas are classified into astrocytomas, oligoastrocytomas and oligodendrogliomas of grade II, grade III and glioblastoma based on the 2007 WorldHealth Organization (WHO) Classification of Tumors of the Central Nervous System [1]
To test the impact of IDH1-R132H and alphathalassemia/mental retardation syndrome X-linked (ATRX) on routine diagnostic neuropathology and their evaluation for progression of gliomas, we analyzed a series of 211 serial sampling of glioma tissues, including 103 astrocytomas (A, anaplastic astrocytoma (AA)), 25 oligodendrogliomas (O, anaplastic oligodendroglioma (AO)), 123 oligoastrocytomas (OA, anaplastic oligoastrocytoma (AOA)) and 181 glioblastomas by immunohistochemistry for IDH1-R132H and ATRX evaluation
In the light of the “ISN-Haarlem” consensus, the routine approach to all diffuse astrocytic and oligodendroglial gliomas begins with performing IHC for ATRX and IDH1-R132H expression
Summary
Diffuse gliomas are classified into astrocytomas, oligoastrocytomas and oligodendrogliomas of grade II, grade III and glioblastoma based on the 2007 WorldHealth Organization (WHO) Classification of Tumors of the Central Nervous System [1]. Patients with low grade gliomas (LGGs, grade II) [2] have a more favorable prognosis than patients with high grade gliomas (grade III and IV), in 50–75% of patients with www.impactjournals.com/oncotarget low grade gliomas, the tumors grow continuously and tend to progress to a higher grade, leading to neurological disability and to death [3]. According to the “ISN-Haarlem” consensus [10], the “integrated” diagnosis was recommended based on histology and stepwise analysis with initial immunohistochemistry for ATRX and IDH1-R132H followed by chromosome 1p/19q status analysis and IDH sequencing [11]. The result will help to evaluate the progressive pattern and time interval of patients with the initial gliomas using the reference histology combined with IDH1-R132H and ATRX status
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