title: Pathological effects of prostate cancer correlate with neuroendocrine differentiation and PTEN expression after bicalutamide monotherapy.
abstract: OBJECTIVE
  Androgen deprivation therapy is the primary treatment for advanced prostate cancer but many patients eventually experience progression to hormone refractory status. Understanding the molecular changes after androgen deprivation therapy would help evaluate the efficacy or failure of second line therapies. Therefore, we analyzed the expression of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), the human epidermal receptor-2 and neuroendocrine differentiation after bicalutamide monotherapy, which is emerging as an alternative treatment for locally advanced prostate cancer.
  
  
  METHODS
  Molecular arrangements were evaluated in 107 radical prostatectomy specimens from patients given 150 mg bicalutamide before surgery. Pathological regressive changes, and the correlation of postoperative biochemical failure with the extent of molecular arrangements and pathological effects were analyzed.
  
  
  RESULTS
  Patients with minimal regression effects after bicalutamide therapy had advanced pathological stage disease, and tended to have positive chromogranin A expression and PTEN inactivation. Only 4 (3.7%) prostatectomy specimens showed human epidermal receptor-2 immunostaining. The probability of positive chromogranin A expression in the PTEN inactivation group was 2.5-fold (OR 2.5, 95% CI 1.1-5.6, p = 0.023) higher than in the nonPTEN inactivation group. Cox regression analysis revealed that seminal vesicle invasion, PTEN/chromogranin A expression and lymph node invasion were significant variables for time to biochemical recurrence.
  
  
  CONCLUSIONS
  PTEN inactivation and neuroendocrine differentiation were related to refractoriness to bicalutamide therapy. These results support the hypothesis that neuroendocrine differentiation is caused by activation of the serine threonine kinase Akt pathway, which results from PTEN inactivation.
authors.affiliation: Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Ham
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Kim
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Ju
authors.forename: Jin Sun
authors.initials: JS
authors.lastname: Lee
authors.forename: Young Deuk
authors.initials: YD
authors.lastname: Choi
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D014105:Tosyl Compounds / Q000627:therapeutic use*
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human