New Prostate Cancer Marker, AZGP1, May Identify Prostate Cancer Likely To Spread
October 4, 2006. Australian prostate cancer researchers have discovered a new genetic marker for identifying aggressive prostate tumors at the time of surgery.
"We have discovered that men who have low levels of a marker called AZGP1 in the prostate at the time of surgery, have a greatly increased risk of developing metastatic cancer, " says Sue Henshall, who leads the prostate cancer research group at Sydney's Garvan Institute.
"This means two things," Henshall says. "These men could benefit from more aggressive treatment such as radiotherapy or chemotherapy around the time of surgery when they still have potentially curable cancer. And patients with a low risk of developing metastatic disease will have the option of deferring treatments that have a negative impact on quality of life."
The next step is to explore the relationship between low levels of AZGP1 and the development of metastatic cancer in other groups of men with prostate cancer (i.e. other prostate cancer tissue banks).
"It is important to begin testing for this marker now because in the next decade, when the outcomes for some of these new patients is known, we will be able to see just how predictive our marker is in the clinic", said Garvan's Cancer Program Director Professor Rob Sutherland.
AZGP stands for Zinc-alpha2-glycoprotein 1. Zinc-alpha2-glycoprotein
is widely distributed in healthy body fluids and body tissues. Previously, types of Zinc-alpha2-glycoprotein have been identified as markers of differentiation in oral, lung and breast tumors. In addition, Zinc-alpha2-glycoprotein (ZAG) is under investigation as a lipid mobilizing factor up-regulated in the rapid weight loss condition in advanced cancer called cancer cachexia.
Other markers for prostate cancer:
Activated Stat5 protein in prostate cancer can predict outcome: A new tumor marker for aggressive prostate cancer and a new target for therapies. 2005
Prostate Cancer Marker, EPCA, Could Find Disease Five Years Earlier. 2005 (update).
Sources and links
Zinc-alpha2-glycoprotein Expression as a Predictor of Metastatic Prostate Cancer Following Radical Prostatectomy
Journal of the National Cancer Institute, Vol. 98, No. 1 9, 1 420- 1 424, October 4, 2006. Susan M. Henshall, et al.
ABSTRACT
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 ci="2.6" to p>
Among the 17 patients in the cohort in whom clinical recurrence was associated with short PSADT [PSA doubling time], 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.
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).
This work was the result of a $3.7 million Program Grant from the Cancer Institute NSW to identify risk in prostate cancer.
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Sue Henshall's prostate cancer group page at Garvan Institute.
Related research articles:
The role of glucocorticoids in the induction of zinc-alpha2-glycoprotein expression in adipose tissue in cancer cachexia. Russell ST, et al. Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, UK. Br J Cancer. 2005 Mar 14;92(5):876-81.
Stage-dependent increase of orosomucoid and zinc-alpha2-glycoprotein in urinary bladder cancer. Irmak S , et al. Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Proteomics. 2005 Nov;5(16):4296-304.
Zinc-a2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Chen Bing, et al. Neuroendocrine and Obesity Biology Unit, Department of Medicine, University Clinical Departments, University of Liverpool, Liverpool L69 3GA, United Kingdom. Proc Natl Acad Sci U S A. 2004 February 24; 101(8): 2500-2505.
Zinc-alpha2-glycoprotein expression as a marker of differentiation in human oral tumors. Brysk et al, Department of Dermatology, University of Texas Medical Branch, Galveston 77555, USA. Cancer Lett. 1999 Mar 22;137(1):117-20.
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This page made and last edited by J. Strax, October 4, 2006.
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