Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis

• Published in: The Prostate 2008-09, Vol.68 (13), p.1396-1404
• Main Authors: Hall, Christopher L., Daignault, Stephanie D., Shah, Rajal B., Pienta, Kenneth J., Keller, Evan T.
• Format: Article
• Language: English
• Subjects: beta Catenin - metabolism; Biomarkers, Tumor - metabolism; Biopsy; bone; Bone Neoplasms - metabolism; Bone Neoplasms - secondary; Disease Progression; DKK-1; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Kaplan-Meier Estimate; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Male; metastasis; Neoplasm Metastasis; Prognosis; prostate cancer; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Retrospective Studies; Soft Tissue Neoplasms - secondary; Tissue Array Analysis; Wnt
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20805

BACKGROUND Prostate cancer (PCa) frequently metastasizes to the bone and induces osteoblastic lesions. We previously demonstrated through over‐expression of the Wnt inhibitor dickkopf‐1 (DKK‐1) that Wnts contribute to the osteoblastic component of PCa osseous lesions in vivo. METHODS To test the clinical significance of DKK‐1 expression during PCa progression, tissue microarrays were stained for DKK‐1 protein by immunohistochemistry. RESULTS DKK‐1 expression index (EI) was found to increase in PIN and primary lesions compared to non‐neoplastic tissue (106 ± 10 vs. 19 ± 6, respectively, where the EI is the product of the percent expression and staining intensity). DKK‐1 expression was also found to be higher in all PCa metastatic lesions (56 ± 21 EI) compared to non‐neoplastic tissues but was significantly decreased versus primary PCa lesions (P