Cathepsin K Expression in Castration-Resistant Prostate Carcinoma: A Therapeutical Target for Patients at Risk for Bone Metastases. Issue 2 (April 2017)

• Record Type: Journal Article
• Authors: Munari, Enrico; Cima, Luca; Massari, Francesco; Bertoldo, Francesco; Porcaro, Antonio Benito; Caliò, Anna; Riva, Giulio; Ciocchetta, Elisa; Ciccarese, Chiara; Modena, Alessandra; Iacovelli, Roberto; Sava, Teodoro; Eccher, Albino; Ghimenton, Claudio; Tortora, Giampaolo; Artibani, Walter; Novella, Giovanni; Bogina, Giuseppe; Zamboni, Giuseppe; Sanguedolce, Francesca; D'Amuri, Alessandro; Martignoni, Guido; Brunelli, Matteo
• Is Part Of: International journal of biological markers. Volume 32:Issue 2(2017)
• Page Start: 243
• Page End: 247
• Publication Date: 2017-04
• Subjects: Bone metastases -- Castration-resistant prostate carcinoma -- Cathepsin K -- RANKL/RANK pathway -- Targeted therapy; Cell receptors -- Periodicals; Histochemistry -- Periodicals; Tumor markers -- Periodicals; Tumor antigens -- Periodicals; 616.99407582
• DOI: 10.5301/jbm.5000246
• Languages: English
• ISSNs: 0393-6155

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.