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Collagen XXIII Expression Is Associated with Prostate Cancer Recurrence and Distant Metastases

Authors' Affiliations: ¹ Vascular Biology Program, Department of Surgery, Children's Hospital; ² Department of Pathology, Brigham and Women's Hospital; ³ Departments of Orthopedic Surgery and Biostatistics, Children's Hospital, Harvard Medical School; ⁴ Department of Urology, Massachusetts General Hospital, Boston, Massachusetts; and ⁵ Department of Urology, University Hospital, Ulm, Germany

Requests for reprints: Bruce R. Zetter, Vascular Biology Program, Department of Surgery, Karp Family Research Laboratories, 11.125, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115. Phone: 617-919-2320; Fax: 617-730-0268; E-mail: bruce.zetter{at}childrens.harvard.edu.

Purpose: We had previously identified a new transmembrane collagen, type XXIII, in metastatic rat prostate carcinoma cells. The purpose of this study was to determine the expression of collagen XXIII in human prostate cancer and investigate its relationship with disease progression.

Experimental Design: We investigated collagen XXIII expression in prostate cancer tissue and did a retrospective analysis of association with prostate-specific antigen (PSA)–defined disease recurrence. The presence of collagen XXIII in prostate cancer patient urine was also assessed before and after prostatectomy.

Results: Collagen XXIII protein was detected at very low levels in benign prostate tissue and was significantly increased in prostate cancer. Distant metastases exhibited significantly higher collagen XXIII levels compared with either localized prostate cancer or regional (lymph node) metastases. Patients with high collagen XXIII levels had a 2.8-fold higher risk of PSA failure with median time to failure of 8.1 months, compared with low collagen XXIII patients with a median time to failure of 5 years. Multivariate Cox regression showed that the presence of collagen XXIII was significantly associated with time to PSA recurrence, independent of other clinical variables. Collagen XXIII was also detected in prostate cancer patient urine, with reduced levels after prostatectomy, indicating potential as a noninvasive fluid biomarker.

Conclusions: We present the first report demonstrating increased collagen XXIII expression in prostate cancer tissue. We show that collagen XXIII level is a significant independent predictor of PSA-defined disease recurrence, suggesting a potential role as a molecular biomarker of prostate cancer progression and metastasis.