ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors.

Jinquan Cai,Chuanbao Zhang,Guanzhang Li,Yongli Li,Zhiliang Wang,Zenghui Qian,Wei Zhang,Kun Yao,Chuanlu Jiang,Tao Jiang,Guangzhi Wang

doi:10.18632/oncoscience.317

Abstract

Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. Malignant astrocytic tumors such as glioblastoma (GBM) are the most lethal intracranial tumors. However, the clinical practicability and significance of molecular parameters for the diagnostic and prognostic prediction of astrocytic tumors is still limited. In this study, we detected ATRX, IDH1-R132H and Ki-67 by immunohistochemistry and observed the association of IDH1-R132H with ATRX and Ki-67 expression. There was a strong association between ATRX loss and IDH1-R132H (p<0.0001). However, Ki-67 high expression restricted in the tumors with IDH1-R132H negative (p=0.0129). Patients with IDH1-R132H positive or ATRX loss astrocytic tumors had a longer progressive- free survival (p<0.0001, p=0.0044, respectively). High Ki-67 expression was associated with shorter PFS in patients with astrocytic tumors (p=0.002). Then we characterized three prognostic subgroups of astrocytic tumors (referred to as A1, A2 and A3). The new model demonstrated a remarkable separation of the progression interval in the three molecular subgroups and the distribution of patients’ age in the A1-A2-A3 model was also significant different. This model will aid predicting the overall survival and progressive time of astrocytic tumors’ patients.

Highlights

Astrocytic tumors are the most common group of human gliomas with inherent tendency for recurrence and malignant progression [1]
ATRX nuclear protein, IDH1-R132H and Ki-67 was detected by immunohistochemistry
IDH1R132H dominated in diffuse astroctytoma (29/50, 58%) and anaplastic astrocytoma (5/9, 55.6%) compared with in primary GBMs (9/58, 15.5%) (Figure 1A; Table 1, p

Summary

Introduction

Astrocytic tumors are the most common group of human gliomas with inherent tendency for recurrence and malignant progression [1]. Several teams demonstrated that IDH mutations and ATRX status, combined with other classical biomarkers, refined the molecular classification of adult gliomas, providing a prognostic tool for clinicians [7,8,9,10,11]. These studies supported the development of a new molecular classification of IDH1-R132H and loss of ATRX, in that the clinical characteristics and prognosis of patients with grade II/III glioma and GBM are not accurately reflected by histological classifications [8, 9, 11,12,13]. We detected ATRX, IDH1-R132H and Ki-67 by immunohistochemistry and characterized three prognostic subgroups of astrocytic tumors (referred to as A1, A2 and A3)

Methods

Results

Conclusion