BCL-2 and p53 expression in clinically localized prostate cancer predicts response to external beam radiotherapy

J Urol. 1999 Jul;162(1):12-6; discussion 16-7. doi: 10.1097/00005392-199907000-00003.

Abstract

Purpose: 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.

Materials and 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.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / radiotherapy*
  • Aged
  • Humans
  • Immunohistochemistry
  • Logistic Models
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / radiotherapy*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53