The ability of biomarkers to predict systemic progression in men with high-risk prostate cancer treated surgically is dependent on ERG status.
The objective of this study was to assess the relationship of the tumor protein levels of TOP2A and MIB-1 and ERG status with cancer-specific outcomes in men with high-risk prostate cancer treated by radical prostatectomy (RP). A 150-pair case-control study was designed from RP patients who developed systemic progression (SP) within 6 years of RP (cases) and men who were free of disease at least 8 years after RP (controls). The cases and controls were matched on conventional prognostic clinical parameters. TOP2A and MIB-1 levels were assessed by immunohistochemical methods, and ERG status was assessed by quantitative reverse transcription-PCR. The prognostic abilities of TOP2A and MIB-1 were significantly better in ERG(-) patients, and TOP2A was superior to MIB-1. In receiver operating characteristic analysis, the TOP2A and MIB-1 scores exhibited AUCs of 0.81 and 0.78 for ERG(-) patients, versus 0.67 and 0.68 for ERG(+) patients, respectively. Clinical parameters attained an AUC of 0.65 in ERG(-) patients and 0.54 in ERG(+) patients. When both markers were incorporated into a model for ERG(-) patients, the AUC increased to 0.83, with TOP2A showing a stronger association with SP than MIB-1. The time to SP was significantly associated with TOP2A; higher 5-year SP rates were observed in patients with higher TOP2A protein levels. In addition, although patient numbers are small, the response to adjuvant androgen deprivation therapy is associated with ERG status, showing more significant treatment effect in ERG(+) patients.
Department of Urology, Laboratory Medicine and Pathology, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. karnes.r@mayo.edu
R Jeffrey
RJ
Karnes
John C
JC
Cheville
Cristiane M
CM
Ida
Thomas J
TJ
Sebo
Asha A
AA
Nair
Hui
H
Tang
Jan-Marie
JM
Munz
Farhad
F
Kosari
George
G
Vasmatzis
D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000032:analysis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D019394:Ki-67 Antigen; D000075223:Poly-ADP-Ribose Binding Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D017430:Prostate-Specific Antigen; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human