Relationship between changes in prostate cancer cell proliferation, apoptotic index, and expression of apoptosis-related proteins by neoadjuvant hormonal therapy and duration of such treatment

Urology. 2005 Jun;65(6):1238-43. doi: 10.1016/j.urology.2005.01.028.

Abstract

Objectives: To investigate the relationships between changes in the carcinoma cell proliferation index, apoptotic index (AI), and apoptosis-related factors, including bcl-2 and bax, after different durations of neoadjuvant hormonal therapy (NHT) in prostate cancer tissue.

Methods: Pre- and post-NHT specimens were obtained from 42 patients who had undergone NHT and radical prostatectomy. The patients were divided into two groups according to the duration of NHT: group 1 (3 to 7 months, n = 21) and group 2 (8 to 12 months, n = 21; no randomization). Immunohistochemistry was used to determine the expression of bcl-2 and bax and to determine the proliferation index, and the terminal deoxynucleotidyl transferase-mediated nick end-labeling method was used to assess apoptosis and determine the AI.

Results: The median proliferation indexes of groups 1 (1.8%) and 2 (1.6%) were significantly lower than the respective values in the pre-NHT specimens (4.9%, P < 0.01). The median AI of group 1 (2.5%) was greater than in the pre-NHT specimens (1.4%). In addition, the post/pre-NHT AI ratio correlated significantly with the duration of NHT in group 1 (r = 0.58, P < 0.01), but not in group 2. Bax expression increased in a manner parallel to that of the AI.

Conclusions: NHT suppresses prostate cancer cell proliferation for 3 to 12 months. Although the AI was increased during 3 to 7 months of NHT, no significant difference was found between the pre-NHT levels and those after 8 to 12 months. Our results support the current belief that the optimal duration of NHT is longer than 3 months.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Apoptosis*
  • Cell Proliferation*
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Neoadjuvant Therapy*
  • Prostatectomy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / therapy
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Antineoplastic Agents, Hormonal
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein