Bad expression influences time to androgen escape in prostate cancer.
OBJECTIVE
To assess the role of selected downstream Bcl-2 family members (Bad, Bax, Bcl-2 and Bcl-xL) in the development of androgen-independent prostate cancer (AIPC), as androgen-deprivation therapy is the treatment of choice in advanced prostate cancer, yet patients generally relapse and progress to an AI state within 18-24 months.


METHODS
The patient cohort was established by retrospectively selecting patients with prostate cancer who had an initial response to androgen-deprivation therapy, but subsequently relapsed with AIPC. In all, 58 patients with prostate cancer were included with matched androgen-dependent (AD) and AI prostate tumours available for immunohistochemical analysis; two independent observers using a weighted-histoscore method scored the staining. Changes in Bad, Bax, Bcl-2 and Bcl-xL expression during transition to AIPC were evaluated and then correlated to known clinical variables.


RESULTS
High Bad expression in AD tumours was associated with an increased time to biochemical relapse (P = 0.007) and a trend towards improved overall survival (P = 0.053). There were also trends towards a decrease in Bad (P = 0.068) and Bax (P = 0.055) expression with progression to AIPC. There were no significant results for Bcl-2 or Bcl-xL.


CONCLUSIONS
There is evidence to suggest that Bad expression levels at diagnosis influence time to biochemical relapse and overall survival, and that levels of pro-apoptotic proteins Bad and Bax fall during AIPC development. Bad might therefore represent a possible positive prognostic marker and potential therapeutic target for AIPC in the future.
Teo
Katy
K
University of Glasgow, Division of Cancer Sciences and Molecular Pathology, Glasgow, Strathclyde, UK.
Gemmell
Lisa
L
Mukherjee
Rono
R
Traynor
Pamela
P
Edwards
Joanne
J
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000378:metabolism*; D015331:Cohort Studies; D019254:Genes, bcl-2 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D017211:Treatment Failure
D000726:Androgen Antagonists; D000728:Androgens; D019253:Proto-Oncogene Proteins c-bcl-2