title: Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer.
abstract: Heat shock proteins (HSPs) protect cells against stress-associated injury and are overexpressed in several malignant tumors. We aimed to investigate their value as prognostic markers in prostate cancer. A tissue microarray (TMA) was constructed of 289 prostate cancers from radical prostatectomy (RP) specimens with median follow-up of 48.9 months. Slides were immunostained for HSP27, HSP60 and HSP70. Intensity and extent of immunoreactivity (IR) and their product (IRp) was evaluated by two observers. The IRp of HSP27 and HSP60, but not of HSP70, significantly predicted biochemical recurrence (p=0.014, 0.034 and 0.160, respectively). Recurrence-free survival in patients with strong HSP27 and HSP60 staining was shorter than in those with weak expression (p=0.019 and 0.001, respectively). IRp of HSP27 and HSP60 correlated with Gleason score (p<0.01). HSP60 was an independent predictor of biochemical recurrence in multivariate analysis, including extraprostatic extension, margin status, seminal vesicle invasion and Gleason score. Weighted kappa for interobserver agreement of HSP27, HSP60 and HSP70 IR was 0.613-0.823 for intensity and 0.584-0.719 for IRp, but only 0.036-0.244 for extent, raising the question whether staining extent should be estimated on TMA. We conclude that HSP27 and HSP60 are predictors of biochemical recurrence after RP.
authors.affiliation: Department of Oncology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Axel
authors.initials: A
authors.lastname: Glaessgen
authors.forename: Sara
authors.initials: S
authors.lastname: Jonmarker
authors.forename: Anna
authors.initials: A
authors.lastname: Lindberg
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.forename: Rolf
authors.initials: R
authors.lastname: Lewensohn
authors.forename: Peter
authors.initials: P
authors.lastname: Ekman
authors.forename: Alexander
authors.initials: A
authors.lastname: Valdman
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018834:Chaperonin 60 / Q000032:analysis / Q000378:metabolism*; D018572:Disease-Free Survival; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D018834:Chaperonin 60; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D017430:Prostate-Specific Antigen