title: The utility of tissue transglutaminase as a marker of apoptosis during treatment and progression of prostate cancer.
abstract: OBJECTIVE
  To determine the extent of cell proliferation and apoptosis during treatment and progression of prostate cancer and to determine whether staining for tissue transglutaminase is a better histological marker than TUNEL for neoadjuvant androgen ablation treatment of localized prostate cancer.
  
  
  METHODS
  Immunocytochemistry techniques were used on archival prostate tissue from four groups of men: 14 men with BPH, 18 men with untreated, localized prostate cancer, 21 men with localized prostate cancer who received neoadjuvant hormone therapy prior to prostatectomy and 18 men with metastatic androgen-independent prostate cancer. Cell proliferation was evaluated by staining for the Ki67 nuclear antigen, and apoptosis was evaluated by staining for DNA fragmentation (TUNEL technique) and tissue transglutaminase (tTG). Image analysis was used to quantitate the results.
  
  
  RESULTS
  TUNEL staining increased by 37% in localized prostate cancer compared with BPH, with a further increase of 43% seen after neoadjuvant therapy, although variation was such that neither was statistically significant. In androgen-independent cancer, TUNEL staining was decreased compared with neoadjuvant hormone treated cancer (p = 0.02). Staining for tTG was not increased in untreated prostate cancer compared with BPH; however, staining more than doubled after neoadjuvant therapy, compared with untreated prostate cancer (p = 0.04). Staining for tTG was markedly decreased in androgen-independent cancer (p = 0.07 compared with BPH and p = 0.0004 compared with neoadjuvant hormone treated cancer). Ki67 immunoreactivity did not significantly change in localized prostate cancer, either before or after neoadjuvant therapy, compared with BPH, but it more than doubled in androgen-independent prostate cancer (p = 0.07 compared with BPH and p = 0.05 compared with untreated prostate cancer).
  
  
  CONCLUSIONS
  This study shows that cell proliferation increases and apoptosis decreases as prostate cancer progresses to androgen independence, and, that of the markers used in this study, tissue transglutaminase most accurately reflects the anticipated effect of neoadjuvant hormone therapy on localized prostate cancer. An assessment of these parameters provides a valuable tool for appraising new prostate cancer therapies.
authors.affiliation: Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: R S
authors.initials: RS
authors.lastname: Rittmaster
authors.forename: L N
authors.initials: LN
authors.lastname: Thomas
authors.forename: A S
authors.initials: AS
authors.lastname: Wright
authors.forename: S K
authors.initials: SK
authors.lastname: Murray
authors.forename: K
authors.initials: K
authors.lastname: Carlson
authors.forename: R C
authors.initials: RC
authors.lastname: Douglas
authors.forename: J
authors.initials: J
authors.lastname: Yung
authors.forename: M
authors.initials: M
authors.lastname: Messieh
authors.forename: D
authors.initials: D
authors.lastname: Bell
authors.forename: C B
authors.initials: CB
authors.lastname: Lazier
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002455:Cell Division; D053938:DNA Fragmentation; D018450:Disease Progression; D019204:GTP-Binding Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009362:Neoplasm Metastasis; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins