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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.

Int J Biol Markers 2017; 32(2): e243 - e247

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/jbm.5000246

Authors

Enrico Munari, Luca Cima, Francesco Massari, Francesco Bertoldo, Antonio Benito Porcaro, Anna Caliò, Giulio Riva, Elisa Ciocchetta, Chiara Ciccarese, Alessandra Modena, Roberto Iacovelli, Teodoro Sava, Albino Eccher, Claudio Ghimenton, Giampaolo Tortora, Walter Artibani, Giovanni Novella, Giuseppe Bogina, Giuseppe Zamboni, Francesca Sanguedolce, Alessandro D’Amuri, Guido Martignoni, Matteo Brunelli

Article History

Disclosures

Financial support: This study was supported by internal funding from the Department of Diagnostics and Public Health, University of Verona (MB, FUR 2014).
Conflict of interest: The authors declare that they have no competing financial interests.

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Authors

Affiliations

  • Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy
  • Anatomic Pathology, Sacro Cuore Don Calabria Hospital, Negrar (Verona) - Italy
  • Medical Oncology, University and Hospital Trust, Verona - Italy
  • Internal Medicine, University and Hospital Trust, Verona - Italy
  • Urology Clinic, University and Hospital Trust, Verona - Italy
  • Medical Oncology, Camposampiero-Cittadella Hospitals, Padova - Italy
  • Department of Pathology, University and Hospital Trust, Riuniti Hospital, Foggia - Italy
  • Anatomic Pathology, Cardinale Giovanni Panico Hospital, Tricase (Lecce) - Italy
  • Anatomic Pathology, Pederzoli Hospital, Peschiera del Garda (Verona) - Italy

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