© The Author 2006. Published by Oxford University Press.
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Zinc-alpha2-glycoprotein Expression as a Predictor of Metastatic Prostate Cancer Following Radical Prostatectomy
Affiliations of authors: Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, Sydney, Australia (SMH, LGH, SAE, AVB, JGK, RLS); Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia (LGH); Department of Tissue Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Australia (JGK); Division of Oncology, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (DIQ); Department of Urology (PDS) and Department of Medical Oncology (JJG), St Vincent's Hospital, Darlinghurst, Sydney, Australia; Division of Surgery, Bankstown Hospital, Bankstown, NSW, Australia (AVB)
Correspondence to: Susan M. Henshall, PhD, Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia (e-mail: s.henshall{at}garvan.org.au).
The risk of metastatic progression for prostate cancer patients who undergo radical prostatectomy is best estimated presently based on prostate-specific antigen (PSA) doubling time (PSADT). However, additional markers of risk are needed to identify patients who may benefit from aggressive salvage treatment. A decrease in zinc-alpha2-glycoprotein (AZGP1) mRNA levels in malignant prostate epithelium was previously shown to predict biochemical recurrence, as defined by rising levels of serum PSA after radical prostatectomy. We assessed the reliability with which AZPG1 expression could predict clinical recurrence and metastatic progression. Using immunohistochemical methods, we analyzed AZPG1 expression in malignant prostate epithelium in prostatectomy specimens from 228 prostate cancer patients. Low (i.e., absent or weak) AZGP1 expression was associated with clinical recurrence (defined as confirmed localized recurrence, metastasis, or death from prostate cancer; hazard ratio [HR] = 4.8, 95% confidence interval [CI] = 2.2 to 10.7, P<.001) and with bony metastases or death from prostate cancer (HR = 8.0, 95% CI = 2.6 to 24.3, P<.001). Among the 17 patients in the cohort in whom clinical recurrence was associated with short PSADT, absent or weak AZGP1 expression was observed in 13 patients. If these preliminary findings are validated in independent cohorts, the measurement of AZGP1 levels in radical prostatectomy specimens may permit an accurate and timely assessment of risk of metastatic progression after radical prostatectomy.
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