title: Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression.
abstract: OBJECTIVE
  Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed.
  
  
  METHODS
  Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time.
  
  
  RESULTS
  In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022).
  
  
  CONCLUSIONS
  During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.
authors.affiliation: Department of Urology, LKH Graz, Medical University of Graz, Graz, Austria. herbert.augustin@meduni-graz.at
authors.forename: H
authors.initials: H
authors.lastname: Augustin
authors.forename: C
authors.initials: C
authors.lastname: Freibauer
authors.forename: L
authors.initials: L
authors.lastname: Bayer
authors.forename: G
authors.initials: G
authors.lastname: Lunglmayr
authors.forename: F
authors.initials: F
authors.lastname: Tschurlovich
authors.forename: W
authors.initials: W
authors.lastname: Kuber
authors.forename: K
authors.initials: K
authors.lastname: Pummer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D017273:Goserelin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014105:Tosyl Compounds; D028761:Withholding Treatment
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D014408:Biomarkers, Tumor; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; D013739:Testosterone; C053541:bicalutamide