Abstract 572: Reduced AZGP1 expression is an independent predictor of early PSA recurrence and associated with ERG fusion positive, PTEN deleted prostate cancers

Abstract

Abstract Zinc-binding Alpha-2-Glycoprotein 1 (AZGP1) is a soluble protein that is known to stimulate lipid degradation in adipocytes. AZGP1 is physiologically expressed in various normal tissues including several types of secretory epithelial cells like breast cells, prostate cells and liver cells, and deregulated expression has been reported from several tumor types including breast, uterine cervix, and prostate cancers. In prostate cancer, AZGP1 was suggested as a candidate prognostic biomarker. To thoroughly evaluate the clinical impact of AZGP1 alteration in prostate cancer, we analyzed immunohistochemical AZGP1 expression in a tissue microarray containing 11,152 prostate cancers with attached clinical and molecular data. In addition, we estimated the relationship of AZGP1 expression with key genomic alterations in prostate cancer. For that purpose, we used data on ERG status and PTEN, 3p13, 5q21 and 6q15 deletions from our earlier studies. AZGP1 expression was strong in benign prostatic glands but absent in 38.0% of 8,510 interpretable prostate cancers. Reduced AZGP1 expression was associated with TMPRSS2:ERG fusion detected by FISH and immunohistochemical analysis (p<0.0001 each). For example, AZGP1 immunostaining was absent in 54.6% of 2,029 ERG positive but in only 28.1% of 2,398 ERG negative cancers (p<0.0001). Reduced expression of AZGP1 was tightly linked to high Gleason grade, advanced pathological tumor stage, positive nodal status and early PSA recurrence (p<0.0001) in all cancers, but also in the subgroups of ERG negative and ERG positive cancers. The prognostic role of AZGP1 expression was independent of Gleason grade, pT stage, pN stage, surgical margin status and preoperative PSA, irrespective of whether preoperative or postoperative parameters were used. Reduced AZGP1 expression was strongly associated with PTEN deletions - one of the strongest known molecular prognosticators in prostate cancer (p<0.0001). However, the association of reduced AZGP1 expression with early PSA recurrence was also independent of PTEN deletions. In conclusion, reduced expression of AZGP1 is strongly related to adverse prognostic features in prostate cancer - independent of clinico-pathological findings and PTEN deletions. Citation Format: Maria Christina Tsourlakis, Martina Kluth, Sandra Kleinhaus, Sawinee Masser, Christoph Burdelski, Hartwig Huland, Hans Heinzer, Markus Graefen, Burkhard Beyer, Stefan Steurer, Ronald Simon, Christina Koop, Thorsten Schlomm, Guido Sauter, Sarah Minner. Reduced AZGP1 expression is an independent predictor of early PSA recurrence and associated with ERG fusion positive, PTEN deleted prostate cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 572. doi:10.1158/1538-7445.AM2014-572