Phosphorylated Hsp27 is mutually exclusive with ATRX loss and the IDH1(R132H) mutation and may predict better prognosis among glioblastomas without the IDH1 mutation and ATRX loss

AIM: To identify biomarkers for accurate classification of glioma. PATIENTS AND METHODS: We evaluated the heat shock protein 27 (Hsp27), phosphorylated Hsp27 (p-Hsp27), ATRX and IDH1(R132H)proteins using immunohistochemistry in 421 glioma tissues. The χ(2) test was used to assess the relationship between molecular alterations and clinico-pathological parameters. Kaplan-Meier survival curves were constructed, and differences were detected by the log-rank test. RESULTS: We found that Hsp27 and p-Hsp27 were mainly expressed in aggressive astrocytic gliomas. However, neither Hsp27 nor p-Hsp27 expression was related to survival time for any grade of glioma. Interestingly, p-Hsp27 was mutually exclusive with ATRX loss (ATRX(−)) and the IDH1(R132H) mutation, except for one case of anaplastic astrocytoma. We classified glioblastomas (GBMs) into three subtypes: ATRX(−)/IDH1(R132H), high p-Hsp27 expression (p-Hsp27(+)) and none of these three markers. ATRX(-)/IDH1(R132H)showed the longest median survival (19.6 months). The prognostic difference between p-Hsp27(+) and none of these three markers was significant (15.0 vs 13.1 months, P=0.045). Moreover, p-Hsp27(+) predicted better sensitivity for standard therapy among GBMs without the IDH1 mutation and ATRX loss (26.3 vs 15.5 months, P=0.008). CONCLUSION: p-Hsp27 is a novel biomarker of glioma and might have important clinical value for further classification of patients with wild-type IDH1 and normal ATRX expression, for evaluating prognosis and for guidance for adjuvant therapy.