title: Receptor activator of nuclear factor-kappaB ligand (RANKL) as a novel prognostic marker in prostate carcinoma.
abstract: Combined immunodetection of parathyroid hormone-related protein (PTHrP) and receptor activator of NF-kappaB ligand (RANKL) has shown to successfully distinguish poorly- and well-differentiated prostate carcinoma (PCa). In the present study, we aimed to assess whether immunohistochemical evaluation of these factors, and also osteoprotegerin (OPG) and Ki67, in radical prostatectomy specimens can predict biochemical recurrence. Fifty nine PCa cases undergoing radical prostatectomy between 1995 and 1998, without history of neoadjuvant hormonal therapy, were studied. Preoperative serum prostate-specific antigen (PSA), Gleason-sum score, pathologic stage, perineural invasion, seminal vesicle involvement, and positive surgical margins were assessed in these patients. Biochemical recurrence, defined by PSA > 0.4 ng/mL at 90 days or later after prostatectomy, occurred in 32/59 patients. In these patients, positivity for OPG and RANKL in the tumoral epithelium was higher than in those patients with no biochemical recurrence. Using univariate analysis, Gleason-sum score, surgical margins, and seminal vesicle involvement, as well as OPG and RANKL immunostaining (using a score value corresponding to moderate staining as cut-off) were significant predictors of biochemical recurrence (p<0.05). Using the multivariate Cox model, among the evaluated factors only RANKL expression (hazard ratio 11.6; p <0.001) was an independent prognostic indicator. Our findings suggest that immunohistochemical evaluation of RANKL in the primary tumor is a potential risk factor in PCa patients.
authors: Urology Department, Fundación Jiménez Díaz (Capio Group), Madrid, Spain.
authors: Francisco C
authors: FC
authors: Pérez-Martínez
authors: Verónica
authors: V
authors: Alonso
authors: José L
authors: JL
authors: Sarasa
authors: Félix
authors: F
authors: Manzarbeitia
authors: Remigio
authors: R
authors: Vela-Navarrete
authors: Francisco J
authors: FJ
authors: Calahorra
authors: Pedro
authors: P
authors: Esbrit
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D053245:RANK Ligand / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D044162:Parathyroid Hormone-Related Protein; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D017430:Prostate-Specific Antigen