title: Tissue Chromogranin A Expression during Prostate Cancer Progression: Prediction of Chemosensitivity.
abstract: OBJECTIVE
  We investigated the clinical significance of chromogranin A (CgA) expression as a neuroendocrine (NE) marker during prostate cancer (PCa) progression, especially as a potential predictor of chemotherapeutic response in castration-resistant PCa (CRPC) patients based on immunohistochemical findings.
  
  
  METHODS
  Sixteen CRPC patients who underwent combination (docetaxel/estramustine/ carboplatin; DEC) chemotherapy were retrospectively studied. Immunostaining of CgA was performed using prostate biopsy samples obtained at the initial PCa diagnosis, during androgen deprivation therapy, at the time of CRPC diagnosis, and after 2 cycles of DEC therapy. The positive rate was expressed as the mean percentage of positively stained tumor cells against the total number of tumor cells. Differences in positive rates among the treatment courses were compared using a Mann-Whitney test.
  
  
  RESULTS
  The mean percentage of CgA-positive PCa cells increased in a stepwise manner until CRPC development and then significantly decreased after DEC therapy. Subanalysis of CgA at CRPC diagnosis showed a more evident reduction of CgA expression after DEC therapy in patients who also had a high level of CgA as compared to those with a low CgA level (P = .003). Likewise, longer prostate-specific antigen progression-free survival was related to CRPC and high CgA (P = .028).
  
  
  CONCLUSIONS
  NE differentiation of PCa cells is accelerated despite androgen deprivation and reaches a peak at the time of CRPC diagnosis. Although further studies using larger samples are needed, CgA expression in CRPC may be a candidate tissue biomarker to reflect the chemotherapy sensitivity of individual PCa cells.
authors.affiliation: Department of Urology, Shimane University School of Medicine, 89-1 Enya-cho, 693-8501 Izumo, Japan. mitsui@med.shimane-u.ac.jp.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Mitsui
authors.affiliation: Department of Urology, Shimane University School of Medicine, 89-1 Enya-cho, 693-8501 Izumo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Arichi
authors.affiliation: Department of Urology, Shimane University School of Medicine, 89-1 Enya-cho, 693-8501 Izumo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Hiraki
authors.affiliation: Department of Surgical Pathology, Shimane University School of Medicine, 89-1 Enya-cho, 693-8501 Izumo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Department of Urology, Shimane University School of Medicine, 89-1 Enya-cho, 693-8501 Izumo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yasumoto
authors.affiliation: Department of Urology, Shimane University School of Medicine, 89-1 Enya-cho, 693-8501 Izumo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiina
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D053379:Chromogranin A / Q000096:biosynthesis*; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D004961:Estramustine / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D053379:Chromogranin A; D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D016190:Carboplatin; D017430:Prostate-Specific Antigen