Expression Of Oncogen Erg Is A Prognostic Biomarker In Localized Prostate Cancer Treated With Radiation Therapy

Oncogen ERG is overexpressed at a high proportion (approximately 50%) in patients with localized prostate cancer (PCa) as a result of a gene fusion with the androgen-driven promoter of the TMPRSS2 gene. Initial evidence suggests that TMPRSS2-ERG gene fusion is linked to worse prognosis for clinical events and resistance to chemotherapy in advanced PCa. However, there is little prognostic evidence on TMPRSS2-ERG gene fusion and localized PCa. The aim was to determine whether overexpression of oncogene ERG is a prognostic biomarker for survival in patients (pts) with localized PCa treated with radiation therapy (RT) w/wo androgen deprivation therapy (ADT). Pts with histological diagnosis of prostate adenocarcinoma treated with RT w/wo ADT were included. Immunohistochemistry (IHC) determination of oncogene ERG was performed on paraffin samples from tissue with prostate cancer in all pts at diagnosis. The use of the IRON-EP11 antibody was used to determine the expression of the ERG protein. A positive reaction was considered if tumor cells had a nuclear staining for the ERG-EP11 antibody. Categorical and continuous variables were determined in each group. Survival (ERG+/ERG-) was determined using the Kaplan-Meier, and survival comparisons were made using the log-rank test. The association between prognostic variables and survival was performed by Cox's analysis. Between 2002 and 2006, a total of 127 pts were included. Patient characteristics are summarized in the below Table. More than 85% of patients were intermediate and high risk in both groups. Initial PSA was higher in the ERG+ group (p. 0.025). The rest of the variables were well balanced in both groups. A total of 83/127 pts (65%) expressed ERG protein (EGR+), while 44/127 pts (35%) did not express the ERG protein (EGR-). With a median follow-up of 11 yrs (0.5 - 15.6 years), biochemical free survival (BFS) at 10 yrs was higher in EGR- (p<0.01). EGR- pts had increased metastasis-free survival (MFS) at 10-yrs compared to ERG+ (p<0.014). In MVA analysis, factors related to BF were ERG protein expression (HR 32, 95%IC 11.23 - 73.2, p = 0.03) and high-risk group (HR 6.54, 95%IC 4.32 – 54.76, p = 0.004). In this retrospective cohort study, the expression of oncogene ERG is a prognostic biomarker for BFS and MFS in pts with localized PCa treated with RT.Abstract 4022; TableERG +ERG -P-valueN pts83 pts44 pts0.65Age (yrs) mean84 (65-94)83 (63-95)0.77TT1c T2 T3 T48 (9.6%) 40(48.2%) 33 (39.8%) 2(2.4%)T1c T2 T3 T45(11.3%) 19(43.2%) 19(43.2%) 1(2.3%)0.92NN0 N172(87%) 11(13%)N0 N138(85%) 6(15%)0.85Risk groupLow Intermediate High8(9.6%) 21(25.3%) 54(65.1%)Low Intermediate High3(6.8%) 13(29.5%) 28(63.6%)0.68PSA mean ng/mlDiagnosis Relapse17.22 6.61Diagnosis Relapse10.56 3.470.025 0.313Gleason score6 7 ≥836(43.4%) 31(37.4%) 16(19.2)6 7 ≥820(45.5%) 15(34.1%) 9(20.4%)0.57Androgen deprivationYes No61(73.5%) 22(26.5%)Yes No31(70.5%) 13(29.5%)1Radiation dose≤72Gy >72Gy3(3.6%) 80(96.4%)≤72Gy >72Gy2(4.5%) 42(95.5%)0.43 Open table in a new tab