The Ability of Biomarkers to Predict Systemic Progression in Men with High-Risk Prostate Cancer Treated Surgically Is Dependent on ERG Status

Abstract

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. Cancer Res; 70(22); 8994-9002. ©2010 AACR.

ERG Status Is Unrelated to PSA Recurrence in Radically Operated Prostate Cancer in the Absence of Antihormonal Therapy

“…Attard and colleagues (49) showed that men with androgen-resistant cancers had a higher maximal prostatespecific response when treated with the antiandrogen abiraterone acetate if the tumors were ERG-positive compared with ERG-negative tumors. This is also in the line with a recent study by Karnes and colleagues (50), which showed that patients with ERG-positive tumors showed a more significant treatment effect in response to adjuvant androgen deprivation than patients with ERG-negative tumors. This could be due to the fact that ERG-positive tumors are particularly dependent on a functional AR because ERG can only be overexpressed in the presence of AR.…”

TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

“…In concert with other publications showing the potential predictive value of TMPRSS2-ERG status on ADT response (18,35,36), ERG overexpression was reported to be a factor in the relative response to salvage ADT following surgery (19). However, in our subgroup of patients treated with ADT, neither TMPRSS2-ERG fusion nor ERG overexpression predicted outcome.…”

“…Karnes and colleagues have proposed that ERGpositive patients present a better response to androgen deprivation (36) and, recently, TMPRSS2-ERG status has been shown to be a predictive biomarker for androgen therapy in the form of abiraterone (46). As such, our results could differ in patients receiving combined modality therapy as the primary treatment (e.g., high-risk or locally advanced prostate cancer) in which fusion status could be studied in the context of the need for salvage ADT (including enzalutamide or abiraterone) or systemic chemotherapy.…”

Quantum dot-based immunofluorescent imaging and quantitative detection of TOP2A and prognostic value in triple-negative breast cancer

“…While TOP2A has been extensively studied in tumor samples, such as breast cancer, prostate cancer, gastric cancer, and ovarian cancer, [25][26][27][28] its role in carcinogenesis …”