A prospective multicentre phase III validation study of AZGP1 as a biomarker in localized prostate cancer

Prostate cancers (PCs) with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of PC still lack precision in identifying individuals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are...

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Bibliographic Details
Published in:	Annals of oncology Vol. 28; no. 8; pp. 1903 - 1909
Main Authors:	Zhang, A.Y., Grogan, J.S., Mahon, K.L., Rasiah, K., Sved, P., Eisinger, D.R., Boulas, J., Vasilaris, A., Henshall, S.M., Stricker, P.D., Kench, J.G., Horvath, L.G.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-08-2017
Subjects:	Adipokines Adult Aged AZGP1 Biomarkers, Tumor - metabolism Biopsy Carrier Proteins - metabolism Cohort Studies Glycoproteins - metabolism Humans Male Middle Aged prognosis Prospective Studies prostate cancer Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology protein expression tissue microarray prostate cancer AZGP1 tissue microarray prognosis protein expression
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Summary:	Prostate cancers (PCs) with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of PC still lack precision in identifying individuals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are in clinical practice as they lack rigorous validation. This study prospectively enrolled an independent phase III cohort to evaluate the clinical utility of zinc-alpha 2-glycoprotein (AZGP1) as a prognostic biomarker in localized PC. In our multicentre, prospective phase III study, AZGP1 status in 347 radical prostatectomy specimens was assayed by immunohistochemistry in a NATA-accredited laboratory. The AZGP1 score was assessed in a multivariable model incorporating established prognostic factors. We also report extended outcomes from our previous phase II study. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints were metastasis-free survival (MFS) and PC-specific survival (PCSS). In the phase II cohort, with a median follow-up of 15.8 years, low/absent AZGP1 expression was an independent predictor of poor BRFS (HR, 1.4; 95% CI, 1.1–1.9; P = 0.03), MFS (HR, 2.8; 95% CI, 1.2–6.6;P = 0.02) and PCSS (HR, 3.8; 95% CI, 1.5–9.5;P = 0.005). These results were validated in our prospective phase III cohort. Low/absent AZGP1 expression independently predicted for BRFS (HR, 1.9; 95% CI, 1.1–3.3;P = 0.02), with shorter MFS (HR, 2.0; 95% CI, 1.1–3.4;P = 0.02). AZGP1 improved the discriminatory value when incorporated into existing prognostic risk models. Our study provides prospective phase III validation that absent/low AZGP1 expression provides independent prognostic value in PC. This study provides robust evidence for the incorporation of this biomarker into clinical practice.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0923-7534 1569-8041
DOI:	10.1093/annonc/mdx247