title: Predictive value of PAK6 and PSMB4 expression in patients with localized prostate cancer treated with dose-escalation radiation therapy and androgen deprivation therapy.
abstract: OBJECTIVE
  The present study analyzed the expression by immunochemistry of the novel markers P21-activated protein kinase 6 (PAK6) and proteasome beta-4 subunit (PSMB4) in men with localized prostate cancer (PC) who were treated with dose-escalation radiotherapy (RT) and androgen deprivation therapy.
  
  
  METHODS
  Between 1996 and 2004, a cohort of 129 patients with PC who underwent diagnostic biopsies pretreatment and 24 to 36 months following RT were enrolled in this study. Suitable archival diagnostic tissue was obtained from 89 patients. Median follow-up was 129 months (48-198). Correlation analysis was done to assess association between PAK6 and PSMB4 expression and clinical outcome.
  
  
  RESULTS
  PAK6 and PSMB4 were expressed in the cytoplasm in 62% and 96.7% of diagnostic biopsies, respectively. Increased staining for PAK6 was significantly (P = 0.04) correlated with higher Gleason scores. In the multivariate analysis, the intensity of PSMB4 staining was an independent predictor of local relapse (hazard ratio = 8.6, P = 0.04).
  
  
  CONCLUSIONS
  To our knowledge, this is the first description of PAK6 and PSMB4 expression in the diagnostic specimens of men with PC who were treated with RT. If confirmed by further studies, increased expression of these genes could be used to identify patients at a high risk of developing local failure following high-dose RT, thus better tailoring treatments for the individual patient.
authors.affiliation: Department of Radiation Oncology, La Princesa University Hospital, Madrid, Spain. Electronic address: almudena.zapatero@salud.madrid.org.
authors.forename: Almudena
authors.initials: A
authors.lastname: Zapatero
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Morente
authors.affiliation: Department of Pathology, University Hospital Henares, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Nieto
authors.affiliation: Department of Radiation Oncology, La Princesa University Hospital, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martín de Vidales
authors.affiliation: Department of Pathology, La Princesa University Hospital, Madrid, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Lopez
authors.affiliation: Department of Pathology, La Princesa University Hospital, Madrid, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Adrados
authors.affiliation: Department of Urology, La Princesa University Hospital, Madrid, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Arellano
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Artiga
authors.affiliation: Department of Radiation Oncology, La Princesa University Hospital, Madrid, Spain.
authors.forename: Feliciano
authors.initials: F
authors.lastname: Garcia-Vicente
authors.affiliation: Department of Urology, University Hospital Henares, Madrid, Spain.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Herranz
authors.affiliation: Department of Radiation Oncology, La Princesa University Hospital, Madrid, Spain.
authors.forename: Olwen
authors.initials: O
authors.lastname: Leaman
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015331:Cohort Studies; D003131:Combined Modality Therapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis* / Q000235:genetics; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016019:Survival Analysis; D054462:p21-Activated Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; C429007:PAK6 protein, human; D054462:p21-Activated Kinases; D017430:Prostate-Specific Antigen; C108898:PSMB4 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Androgen deprivation; Molecular marker; PAK6; PSMB4; Prostate cancer; Radiotherapy