title: Absence of Bcl-2 expression favors response to the short-term administration of diethylstilbestrol diphosphate in prostate Cancer.
abstract: BACKGROUND
  Neoadjuvant hormone therapy remains a controversial issue in spite of multiple studies having been performed.
  
  
  METHODS
  We performed short-term (10 days) treatment with diethylstilbestrol (DES) in 30 patients with stages T2 or T3 prostate cancer (PCa). All the patients underwent needle core prostate biopsy before and radical prostatectomy within a month after the start of the endocrine therapy. The histological effects in PCa and the changes in morphological and clinical parameters and their association were elucidated.
  
  
  RESULTS
  Serum PSA (P < 0.001), Ki-67 PI (P = 0.022), and AR (P = 0.002) expression decreased after the treatment. An obvious effect (Grade 1-3) of endocrine treatment was seen in 11 of 30 patients and was associated with a prominent PSA decrease (P = 0.0274) and with older age (P = 0.0026). Pre-treatment specimens from a group without any effects of endocrine therapy had a higher frequency of Bcl-2 positivity (57.9%) compared to the group of Grade 1-3 effects (27.3%). Prostatectomy specimens presented with significantly higher AI in Bcl-2 negative cases (P = 0.0029) and pre treatment Bcl-2 was associated with a higher AI in Grade 1-3 patients (P = 0.0393).
  
  
  CONCLUSIONS
  Older age is a predictor of histological effects in short-term hormone treatment of PCa. A lower Bcl-2 in biopsy specimens presented more frequently in the patients who experienced a prominent effect of endocrine therapy, and it was also useful to predict a significantly higher AI in Grade 1-3 patients. Histological effects are also associated with the PSA decrease, reflecting the clinically meaningful shrinkage of tumors and a decrease of tumor burden.
authors.affiliation: Department of Urology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nagaoka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kurosu
authors.forename: Teruhiro
authors.initials: T
authors.lastname: Nakada
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bilim
authors.forename: Yosihiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001706:Biopsy; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000172:deficiency; D011944:Receptors, Androgen / Q000096:biosynthesis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; D004054:Diethylstilbestrol; C004955:fosfestrol; D017430:Prostate-Specific Antigen