title: Cathepsin K expression in castration-resistant prostate carcinoma: a therapeutical target for patients at risk for bone metastases.
abstract: BACKGROUND
  The lysosomal cysteine protease cathepsin K is involved in bone remodeling and is also expressed in the peritumoral stroma of carcinomas arising from different organs. A new generation of cathepsin K inhibitors blocking the RANKL/RANK pathway are being developed. We sought to investigate cathepsin K expression in a cohort of castration-resistant prostate carcinomas.
  
  
  METHODS
  Sixteen cases of castration-resistant disease with at least 5 years of follow-up were selected from a cohort of 280 patients who underwent surgery. Cathepsin K was evaluated on formalin-fixed and paraffin-embedded tissue microarrays with 5 tissue spots per case. These were scored as high 2+ (≥30% of cells), low 1+ (<30% of cells) or zero (absence), distinguishing tumor cells and peritumoral stroma cells. Low (1+) and absence (0) of scoring were interpreted as negative, and high (2+) as positive.
  
  
  RESULTS
  The castration-resistant group was composed of 15 acinar adenocarcinomas and 1 neuroendocrine carcinoma, and all showed at least Gleason score 8 at prostatectomy. Two out of 16 cases (12%) scored positive for cathepsin K in tumor cells; and 5 of 16 cases (31%) scored positive in peritumoral stroma cells. The neuroendocrine and acinar subtypes of carcinoma with positive immunoexpression in neoplastic cells developed bone metastases after 4 and 5 years, respectively, and subsequently died.
  
  
  CONCLUSIONS
  Patients affected by castration-resistant prostate carcinoma may be tested for cathepsin K, and a positive strong expression (2+) could be a useful predictive biomarker of response to targeted agents, aiding in the selection of patients eligible for these treatments.
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.|Anatomic Pathology, Sacro Cuore Don Calabria Hospital, Negrar (Verona) - Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cima
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona - Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Internal Medicine, University and Hospital Trust, Verona - Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoldo
authors.affiliation: Urology Clinic, University and Hospital Trust, Verona - Italy.
authors.forename: Antonio Benito
authors.initials: AB
authors.lastname: Porcaro
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caliò
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Riva
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ciocchetta
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona - Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona - Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modena
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona - Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Medical Oncology, Camposampiero-Cittadella Hospitals, Padova - Italy.
authors.forename: Teodoro
authors.initials: T
authors.lastname: Sava
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.
authors.forename: Albino
authors.initials: A
authors.lastname: Eccher
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ghimenton
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona - Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Urology Clinic, University and Hospital Trust, Verona - Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Artibani
authors.affiliation: Urology Clinic, University and Hospital Trust, Verona - Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Novella
authors.affiliation: Anatomic Pathology, Sacro Cuore Don Calabria Hospital, Negrar (Verona) - Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bogina
authors.affiliation: Anatomic Pathology, Sacro Cuore Don Calabria Hospital, Negrar (Verona) - Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
authors.affiliation: Department of Pathology, University and Hospital Trust, Riuniti Hospital, Foggia - Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanguedolce
authors.affiliation: Anatomic Pathology, Cardinale Giovanni Panico Hospital, Tricase (Lecce) - Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: D'Amuri
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.|Anatomic Pathology, Pederzoli Hospital, Peschiera del Garda (Verona) - Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D056657:Cathepsin K / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: C534130:CTSK protein, human; D056657:Cathepsin K