title: Expression of p21 cell cycle protein is an independent predictor of response to salvage radiotherapy after radical prostatectomy.
abstract: BACKGROUND
  To assess whether the expression of p21, p27, and p53 could predict biochemical failure in prostate cancer patients treated with neoadjuvant androgen deprivation prior to salvage radiotherapy for a rising post-radical prostatectomy (RP) prostate-specific antigen (PSA).
  
  
  METHODS
  The expression of p21, p27, and p53 was determined by immunohistochemistry in a cohort of 74 formalin-fixed paraffin-embedded prostate cancer samples obtained from RP. Expression of these markers was then correlated with clinicopathological parameters and biochemical failure-free survival after salvage radiotherapy.
  
  
  RESULTS
  Expression of p21, p27, and p53 was observed in 20%, 69%, and 74% of prostate cancer specimens, respectively. Overexpression of p21 correlated with a higher Gleason score (>7) (P = 0.024). Of the three markers, only p21 expression was correlated with PSA failure after radiotherapy (P = 0.034). In multivariate analysis, both positive p21 (P = 0.004) and pre-radiation serum PSA > 1 ng/ml (P < 0.0001) were independent predictors of biochemical failure after salvage radiotherapy. Patients with p21- tumors and a serum PSA level < or = 1 ng/ml before salvage radiotherapy had a biochemical failure-free survival at 5 years of 83%, compared to 16% at 5 years for those patients with either p21+ tumor or a PSA > 1 ng/ml. Patients with both p21+ and a PSA level > 1 ng/ml had a much lower biochemical failure-free survival rate of 25% at only 18 months (P < 0.0001).
  
  
  CONCLUSIONS
  The expression of p21 in prostatectomy specimens could help predict the likelihood of response to salvage radiotherapy, particularly in patients treated before PSA reaches 1 ng/ml.
authors.affiliation: Laboratoire d'Uro-Oncologie Expérimentale, Centre de Recherche en Cancérologie de l'Université Laval, CHUQ-L'Hôtel-Dieu de Québec, Québec, Canada.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rigaud
authors.forename: Rabi
authors.initials: R
authors.lastname: Tiguert
authors.forename: Marc
authors.initials: M
authors.lastname: Decobert
authors.forename: Hélène
authors.initials: H
authors.lastname: Hovington
authors.forename: Eva
authors.initials: E
authors.lastname: Latulippe
authors.forename: Jacques
authors.initials: J
authors.lastname: Laverdiere
authors.forename: Hélène
authors.initials: H
authors.lastname: Larue
authors.forename: Louis
authors.initials: L
authors.lastname: Lacombe
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D011300:Preoperative Care; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D016879:Salvage Therapy; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017430:Prostate-Specific Antigen