title: Enhanced expression of the secreted form of clusterin following neoadjuvant hormonal therapy as a prognostic predictor in patients undergoing radical prostatectomy for prostate cancer.
abstract: The objective of this study was to characterize changes in clusterin expression in prostate cancer before and after neoadjuvant hormonal therapy (NHT), and to assess the prognostic significance of clusterin expression following NHT in patients undergoing radical prostatectomy. Paired needle biopsy and corresponding radical prostatectomy (RP) specimens obtained from 76 patients were analyzed for expression of clusterin protein by immunohistochemical staining with an antibody recognizing all of the clusterin isoforms. RP specimens following NHT demonstrated stronger expression of clusterin than the corresponding needle biopsy specimens. Clusterin protein was present in the cytoplasm of both biopsy and RP specimens; however, there was no nuclear staining identified in any specimens. The expression level of clusterin in biopsy specimens was significantly associated with the biopsy Gleason score, but not with other parameters available before RP. Furthermore, clusterin expression in RP specimens was significantly associated with the preoperative prostate specific antigen value and pathological stage, but not with other pathological factors. Biochemical recurrence-free survival in patients with strong clusterin expression in RP specimens was significantly lower than that in those with weak clusterin expression; however, the level of clusterin expression could not be used as an independent predictor of biochemical recurrence. These findings suggest that despite the lack of independent significance, the expression level of the secreted form of clusterin in prostate cancer tissue after NHT, which may inversely reflect the therapeutic effect of NHT, could be a useful parameter predicting biochemical recurrence in patients undergoing RP.
authors.affiliation: Department of Urology, Hyogo Medical Center for Adults, 13-70 Kitaohji-cho, Akashi 673-8558, Japan. hideakimiyake@hotmail.com
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Muramaki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kurahashi
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.forename: Isao
authors.initials: I
authors.lastname: Hara
mesh_terms: D000368:Aged; D001706:Biopsy; D051152:Clusterin; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery*
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones