title: Hsp27 and its expression pattern in diffusely infiltrating astrocytomas.
abstract: Heat shock protein 27 (Hsp27) is induced by cell stress conditions. In the presence of oxidative stress it functions as an antioxidant. To study the putative expression patterns and clinical significance of Hsp27, we assessed the associations between Hsp27, R132H mutation of Isocitrate dehydrogenase1 (IDH1-R132H), Hypoxia-inducible factor subunit alpha (HIF-1 alpha), Carbonic anhydrase IX (CA IX), and patient prognosis in astrocytic gliomas.
  
  
  
  Tissue micro-array samples of 295 grade II-IV astrocytomas were stained immunohistochemically for Hsp27, IDH1-R132H, HIF-1 alpha, and CA IX. We tested their relationship with clinicopathological features and patient survival.
  
  
  
  There was a significant correlation between Hsp27 expression and increasing WHO grade (p<0.001). Hsp27 expression correlated significantly with IDH1 mutation when studied within the entire cohort (p<0.001) as well as separately in WHO grade II and III tumors (p=0.006 and 0.002, respectively). IDH1 mutation and HIF-1 alpha positive staining were detected simultaneously (p<0.001). In IDH1 mutated tumors, positive HIF-1 alpha staining correlated with CA IX expression (p=0.027), whereas no such correlation was found in IDH1 non-mutated tumors. IDH1 mutation was associated with a low cell proliferation index (p=0.001) and HIF-1 alpha with increasing proliferation (p = 0.003). Hsp27 expression was associated with a shorter rate of patient survival in univariate survival analysis (p=0.001). In multivariate survival analysis, patient age, IDH1 mutation and HIF-1 alpha appeared as independent prognostic factors (p<0.000, <0.000 and 0.011 respectively)
  
  
  
  Hsp27 expression is associated with increasing WHO grade and patient prognosis in astrocytic gliomas. The results suggest that IDH1 mutation may have an effect on the expression pathways of Hsp27 and CA IX.
authors.affiliation: University of Tampere, School of Medicine, Tampere, Finland. katri.s.makela@uta.fi.
authors.forename: Katri S
authors.initials: KS
authors.lastname: Mäkelä
authors.affiliation: Unit of Neurosurgery, and Fimlab Laboratories, Department of Pathology. Tampere University Hospital, Tampere, Finland. joonas.haapasalo@gmail.com.
authors.forename: Joonas A
authors.initials: JA
authors.lastname: Haapasalo
authors.affiliation: Fimlab Laboratories, Department of Pathology. Tampere University Hospital, Tampere, Finland. joanna.ilvesaro@fimlab.fi.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Ilvesaro
authors.affiliation: University of Tampere, School of Medicine, Institute of Biomedical Technology, and Fimlab Laboratories, Department of Pathology. Tampere University Hospital, Tampere, Finland. seppo.parkkila@uta.fi.
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
authors.affiliation: University of Tampere, School of Medicine, and Fimlab Laboratories, Department of Pathology. Tampere University Hospital, Tampere, Finland. timo.paavonen@uta.fi.
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.affiliation: University of Tampere, School of Medicine, and Fimlab Laboratories, Department of Pathology. Tampere University Hospital, Tampere, Finland. hannu.haapasalo@fimlab.fi.
authors.forename: Hannu K
authors.initials: HK
authors.lastname: Haapasalo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D001254:Astrocytoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000473:pathology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D006360:Heat-Shock Proteins; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D060787:Neoplasm Grading; D011379:Prognosis; D046888:Tissue Array Analysis; D059467:Transcriptome; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases