title: Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance.
abstract: OBJECTIVE
  Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are overexpressed in many tumours. We analysed the expression of relevant HSPs and heat shock factor 1 (HSF1) in classical Hodgkin lymphoma (cHL) and their relationship with caspase signalling pathways and patient outcome.
  
  
  RESULTS
  Using tissue microarrays (TMAs), most cases showed strong immunohistochemical expression of HSPs [10, 27, 40, 60, 70, 90, 110, HO1, cell division cycle 37 homolog (CDC37) and HSF1, which points to cHL as a potential candidate to stress-response inhibitors. Active caspases 3, 8 and 9 were detected in 55.1%, 55.4% and 96.2% of cases although cleaved poly (ADP-ribose) polymerase (PARP) was observed in only 16.1%, suggesting an improper functioning of apoptosis. Statistical analysis showed associations of HSP70 with active caspase 3 (P = 0.000); HSP40 with active caspase 9 (P = 0.031) and p53 (P = 0.003); HO1 with p53 (P = 0.006) and p21 (P = 0.005); and p53 with p21 (P = 0.015).
  
  
  CONCLUSIONS
  Correlations between the expression of apoptotic markers and HSPs may suggest a role for the latter in modulating apoptosis in cHL, mainly through the HSP70-HSP40 system, and in the stabilization of p53. Survival analyses showed that absence of active caspase 8 and HO1 had a negative impact in patient outcome.
authors.affiliation: Department of Pathology, Ramón y Cajal University Hospital, IRYCIS, Madrid, Spain. asanton.hrc@salud.madrid.org
authors.forename: Almudena
authors.initials: A
authors.lastname: Santón
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Cosío
authors.forename: Eva
authors.initials: E
authors.lastname: Cristóbal
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pascual
authors.forename: Alfonso
authors.initials: A
authors.lastname: Muriel
authors.forename: José
authors.initials: J
authors.lastname: García-Laraña
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002648:Child; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D020169:Caspases