title: BCL-2 and p53 expression in clinically localized prostate cancer predicts response to external beam radiotherapy.
abstract: OBJECTIVE
  Clinicians have long been hampered by the inability to distinguish patients with localized prostate cancer who will and will not respond to radiotherapy. In a significant proportion of patients therapy fails as determined by increasing posttreatment serum prostate specific antigen (PSA). We evaluated the expression of 2 key regulators of apoptosis, bcl-2 and p53, relative to treatment outcomes in patients who received external beam radiotherapy for clinically organ confined carcinoma of the prostate.
  
  
  METHODS
  Immunohistochemical staining for bcl-2 and p53 on pretreatment needle biopsies was performed in 54 patients who were treated with radiotherapy for localized prostate cancer. Expression was scored using strict criteria. Nadir PSA less than 1 ng./ml. after therapy was considered a successful treatment response.
  
  
  RESULTS
  There was a predominance of stage T1c cancer (74%) with a mean Gleason score of 6.9 and an average pretreatment PSA of 25.3 ng./ml. Overall 54% of the patients did not have a nadir PSA of less than 1 ng./ml. Of the bcl-2 positive cases therapy ultimately failed in 85%. Similarly 88% of the patients with p53 positive biopsies had treatment failure and in all with bcl-2 as well as p53 expression radiotherapy failed. Expression of bcl-2 and p53 was an independent prognostic variable for treatment failure with odds ratios (95% confidence interval) of 7.3 and 10.8, respectively.
  
  
  CONCLUSIONS
  Expression of bcl-2 and p53 was associated with treatment failure after external beam radiation therapy. These findings suggest that bcl-2 and p53 expression in pretreatment biopsies may be helpful for predicting response to definitive radiotherapy.
authors.affiliation: Department of Urology, James Buchanan Brady Foundation, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Scherr
authors.forename: E D
authors.initials: ED
authors.lastname: Vaughan
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.forename: M
authors.initials: M
authors.lastname: Chung
authors.forename: D
authors.initials: D
authors.lastname: Felsen
authors.forename: R
authors.initials: R
authors.lastname: Allbright
authors.forename: B S
authors.initials: BS
authors.lastname: Knudsen
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism* / Q000532:radiotherapy*; D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000532:radiotherapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53