title: Expression of heat shock proteins in medulloblastoma.
abstract: OBJECTIVE
  Medulloblastoma (MB) is the most common malignant brain tumor in children. Heat shock proteins (HSPs) comprise a superfamily of proteins that serve as molecular chaperones and are overexpressed in a wide range of human cancers. The purpose of the present study was to investigate the expression of HSP27 (pSer(82)), HSP27 (pSer(15)), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt by multiplex bead array assay of MBs. The results of HSP and Akt expression were correlated with MB subtype; immunohistochemical expression of Ki-67 index, bcl-2, and p53; and patients' prognosis.
  
  
  METHODS
  The authors retrospectively evaluated 25 children with MB who underwent surgery. Immunohistochemical analysis of Ki-67, p53, and bcl-2 expression was performed in all cases. By using multiplex bead array assay, a simultaneous detection of HSP27 (pSer(82)), HSP27 (pSer(15)), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt was performed.
  
  
  RESULTS
  Medulloblastoma with extensive nodularity had significantly lower HSP27 (pSer(15)) expression (p = 0.039) but significantly higher HSP60 expression (p = 0.021) than classic MB. Large-cell MB had significantly higher HSP70 expression (p = 0.028) than classic MB. No significant difference was found between HSP27 (pSer(82)), HSP40, HSP90-α, Akt, or phospho-Akt expression and MB subtype. Large-cell MBs had significantly higher Ki-67 index compared with classic MBs (p = 0.033). When analyzing all MBs, there was a significant negative correlation between HSP27 (pSer(15)) and Ki-67 index (r = -0.475, p = 0.016); a significant positive correlation between HSP70 expression and Ki-67 index (r = 0.407, p = 0.043); and a significant positive correlation between HSP70 expression and bcl-2 index (r = 0.491, p = 0.023). Patients with large-cell MB had a worse survival than those with classic MB, but the difference did not reach statistical significance (p = 0.076).
  
  
  CONCLUSIONS
  A substantial expression of several HSPs in MB was observed. Given that HSPs represent an attractive strategy for anticancer therapy, further studies, involving larger series of patients, are obviously necessary to clarify the relationship of HSPs with tumor aggressiveness and prognosis.
authors.affiliation: Department of Neurosurgery, Children's Hospital "Agia Sofia," Athens;
authors.forename: George A
authors.initials: GA
authors.lastname: Alexiou
authors.forename: George
authors.initials: G
authors.lastname: Vartholomatos
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Stefanaki
authors.forename: Amalia
authors.initials: A
authors.lastname: Patereli
authors.forename: Lefkothea
authors.initials: L
authors.lastname: Dova
authors.forename: Achilleas
authors.initials: A
authors.lastname: Karamoutsios
authors.forename: George
authors.initials: G
authors.lastname: Lallas
authors.forename: George
authors.initials: G
authors.lastname: Sfakianos
authors.forename: Maria
authors.initials: M
authors.lastname: Moschovi
authors.forename: Neofytos
authors.initials: N
authors.lastname: Prodromou
mesh_terms: D002528:Cerebellar Neoplasms / Q000378:metabolism*; D018834:Chaperonin 60 / Q000378:metabolism; D002648:Child; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D018834:Chaperonin 60; C494647:DNAJB1 protein, human; D055551:HSP27 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; C060293:HSPD1 protein, human; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins