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

J Clin Pathol. 2018 Aug;71(8):702-707. doi: 10.1136/jclinpath-2018-205000. Epub 2018 Mar 17.

Abstract

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 IDH1R132Hproteins using immunohistochemistry in 421 glioma tissues. The χ2 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 IDH1R132H mutation, except for one case of anaplastic astrocytoma. We classified glioblastomas (GBMs) into three subtypes: ATRX-/IDH1R132H, high p-Hsp27 expression (p-Hsp27+) and none of these three markers. ATRX-/IDH1R132Hshowed 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.

Keywords: ATRX; Hsp27; IDH1; glioma; prognosis.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Chi-Square Distribution
  • Female
  • Glioblastoma / enzymology*
  • Glioblastoma / genetics
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • HSP27 Heat-Shock Proteins / analysis*
  • Heat-Shock Proteins
  • Humans
  • Immunohistochemistry
  • Isocitrate Dehydrogenase / analysis*
  • Isocitrate Dehydrogenase / genetics
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Chaperones
  • Mutation
  • Neoplasm Grading
  • Phosphorylation
  • Time Factors
  • Tissue Array Analysis
  • X-linked Nuclear Protein / analysis*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • ATRX protein, human
  • X-linked Nuclear Protein