Phosphorylated Hsp27 is mutually exclusive with ATRX loss and the IDH1R132H 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 chi(2) test was used to assess the relationship between molecular alterations and clinicopathological 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