title: Immunohistochemical analysis of low-grade and high-grade prostate carcinoma: relative changes of parathyroid hormone-related protein and its parathyroid hormone 1 receptor, osteoprotegerin and receptor activator of nuclear factor-kB ligand.
abstract: OBJECTIVE
  To investigate multiple bone cytokines produced by prostate carcinoma (PCa) as a novel strategy to differentiate potential aggressiveness in localised PCa using immunohistochemical analysis.
  
  
  METHODS
  A total of 47 cases of PCa undergoing radical prostatectomy or transurethral prostatic resection at our institution (Fundación Jiménez Díaz (Grupo Capio), Madrid, Spain) between January 1991 and June 1998 were identified as low-grade (< or =4; n = 22) or high-grade (> or =7, excluding 7 (3+4) cases; n = 25) PCa according to Gleason grade. PCa specimens were immunostained for: parathyroid hormone (PTH)-related protein (PTHrP), the PTH1 receptor, osteoprotegerin and receptor activator of nuclear factor-kappa B ligand (RANKL), as well as Ki67 (a proliferation marker) and CD34 (an angiogenesis marker).
  
  
  RESULTS
  PCa samples showed an increased immunostaining for both osteoprotegerin and RANKL, associated with tumour grade and PTHrP positivity, in the tumoral epithelium. Using a score value of 4-corresponding to moderate staining - as cut-off, the best sensitivity value was for PTHrP (with C-terminal antiserum C6; 100 %); wheras the best specificity value was for RANKL (95 %).
  
  
  CONCLUSIONS
  All the evaluated factors are overexpressed mainly in the high-grade tumours. Our findings indicate that, in most patients with PCa (with Ki67 values between 1% and 9%), sequential determination of C-terminal PTHrP and RANKL immunoreactivities is a useful approach to discriminate low-grade and high-grade tumours.
authors.affiliation: Fundación Jiménez Díaz (Grupo Capio), Madrid, Spain. fcpmartinez@hotmail.com
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Pérez-Martínez
authors.forename: Verónica
authors.initials: V
authors.lastname: Alonso
authors.forename: José L
authors.initials: JL
authors.lastname: Sarasa
authors.forename: Syon-Ghyun
authors.initials: SG
authors.lastname: Nam-Cha
authors.forename: Remigio
authors.initials: R
authors.lastname: Vela-Navarrete
authors.forename: Félix
authors.initials: F
authors.lastname: Manzarbeitia
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Calahorra
authors.forename: Pedro
authors.initials: P
authors.lastname: Esbrit
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D053244:Osteoprotegerin; C473449:PTH1R protein, human; D044162:Parathyroid Hormone-Related Protein; D053246:Receptor Activator of Nuclear Factor-kappa B; D044168:Receptor, Parathyroid Hormone, Type 1