title: Reduced AZGP1 expression is an independent predictor of early PSA recurrence and associated with ERG-fusion positive and PTEN deleted prostate cancers.
abstract: Zinc-alpha 2-glycoprotein (AZGP1) is involved in lipid metabolism and was suggested as a candidate prognostic biomarker in prostate cancer. To evaluate the clinical impact and relationship with key genomic alterations in prostate cancer, AZGP1 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers. Data on ERG status and PTEN, 3p13, 5q21 and 6q15 deletions were available from 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 TPMRSS2:ERG fusions, both by FISH and immunohistochemical analysis (p < 0.0001 each). For example, AZGP1 was absent in 54.6% of 2,029 ERG IHC positive but in only 28.1% of 2,398 ERG negative cancers. Irrespective of the ERG status, reduced AZGP1 expression was tightly linked to high Gleason score, advanced pathological tumor stage, positive nodal status and early PSA recurrence (p < 0.0001 each). Reduced AZGP1 expression was also strongly associated with PTEN deletions. AZGP1 immunostaining was lacking in 62.7% of 842 PTEN deleted but in only 37.3% of PTEN non-deleted cancers but retained strong prognostic influence in both subgroups (p < 0.0001 each). The prognostic role of AZGP1 expression was also independent of Gleason score, pT stage, pN stage, surgical margin status and preoperative PSA, irrespective of whether preoperative or postoperative variables were used for modeling. In conclusion, the results of our study demonstrate that reduced AZGP1 expression is strongly related to adverse prostate cancer prognosis, independently of established clinic-pathological variables and PTEN deletions.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Burdelski
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kleinhans
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kluth
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hube-Magg
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Koop
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Hamburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Heinzer
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Marx
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wittmer
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Hamburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Hamburg, Germany.|Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
mesh_terms: D054392:Adipokines; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D017353:Gene Deletion; D050939:Gene Fusion; D006023:Glycoproteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000209:etiology*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D054392:Adipokines; D002352:Carrier Proteins; D006023:Glycoproteins; D019394:Ki-67 Antigen; D051059:PTEN Phosphohydrolase; D017430:Prostate-Specific Antigen; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein; C072312:ERG protein, human; C494929:PTEN protein, human
keywords: AZGP1; IHC; TPMRSS2:ERG fusion; prognosis; prostate cancer; tissue microarray