ERG Tumor Type is Less Frequent in High Grade and High Stage Prostate Cancers of Chinese Men.

Background: The incidence of prostatic adenocarcinoma has been rapidly increasing among Chinese men. This alarming trend prompted evaluations of early causal genomic alterations known to drive prostate tumorigenesis. Recurrent activation of the ETS-Related Gene (ERG) by genomic rearrangements is the most recognized early event in prostate cancer. Following the initial detection of ERG rearrangement at gene expression and genomic and levels, development of diagnostic quality antibodies against ERG oncoprotein have streamlined the rapid assessment of ERG frequencies world-wide. Unexpectedly, these studies revealed highest frequencies of ERG among Caucasian descents, lower frequencies among African Americans and even lower prevalence of ERG among Asian men. Objective: To asses in a prospective study ERG frequencies, clinico-pathological and prognostic associations of ERG among prostate cancer patients of the Dalian region of Northeast China, by an established immunohistochemical procedure that have been used in studies world-wide. Methods: Formalin fixed paraffin embedded specimens donated by patients (N=50) diagnosed with prostatic adenocarcinoma who underwent transurethral resection of the prostate (TURP) between 2007 and 2012 were evaluated for ERG by immunohistochemistry. Results: Of the 50 cases, 13/50 (26.0%) tumors were positive for ERG. In all cases, normal prostatic epithelial were ERG negative. ERG was more frequently detected in the lower Gleason score (≤7) and low T-stage. Consistent with reports from Asian countries the results of our study shows lower overall frequencies of ERG positive tumors when compared to reports from Western countries. Conclusion: The intriguing association of even lower ERG frequencies with high Gleason scores and higher T-stages provides impetus for current driver gene discoveries focused on the predominantly ERG negative prostate cancers of Asian men.

Ethnicity and ERG frequency in prostate cancer.

Emerging observations emphasize a distinct biology of prostate cancer among men of different ethnicities and races, as demonstrated by remarkable differences in the frequency of ERG oncogenic activation, one of the most common and widely studied prostate cancer driver genes. Worldwide assessment of ERG alterations frequencies show consistent trends, with men of European ancestry having the highest rates of alteration and men of African or Asian ancestries having considerably lower alteration rates. However, data must be interpreted cautiously, owing to variations in assay platforms and specimen types, as well as ethnic and geographical classifications. Many opportunities and challenges remain in assessing cancer-associated molecular alterations at a global level, and these need to be addressed in order to realize the true potential of precision medicine for all cancer patients.

Predicting Prostate Cancer Progression as a Function of ETS-related Gene Status, Race, and Obesity in a Longitudinal Patient Cohort.

BACKGROUND: ETS-related gene (ERG) oncogenic activation is the most common genomic alteration in prostate cancer (CaP) although it occurs less frequently in African American (AA) versus Caucasian (CA) patients, and the potential role of ERG as a prognostic marker has not been confirmed. OBJECTIVE: This study was conducted to confirm strong racial variation in the prevalence of ERG oncoprotein expression and to examine ERG oncoprotein expression, race, and body mass index as independent and joint predictors of CaP biochemical recurrence (BCR) following radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of CA and AA CaP patients enrolled at Walter Reed National Military Medical Center, who donated clinically annotated, whole-mounted, prostatectomy specimens between 1994 and 2014 following RP, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier (KM) estimation curves and multivariable Cox proportional hazards models were used to examine time to BCR as a function of ERG status, patient race, and obesity. RESULTS AND LIMITATIONS: Among 930 eligible patients (36.1% AA and 63.9% CA), with 155 (16.7%) BCR events and a median follow-up time of 5.1 yr, ERG oncoprotein expression was significantly less prevalent in index tumors of AA versus CA patients (23.2% vs 49.3%; p<0.0001). KM curves showed significantly poorer BCR-free survival for CA patients with ERG-negative index tumors but not for AA patients. Race-stratified multivariable analyses revealed a significant association between ERG-negative index tumors and poorer BCR-free survival among CA patients (hazards ratio=1.67, confidence interval=1.07, 2.61; p=0.024). Less heterogeneity in ERG expression among AA patients may reduce the ability to show its association with BCR. CONCLUSIONS: Striking racial variation in ERG oncoprotein expression was confirmed. A novel observation was the importance of index tumor ERG-negative status in predicting CaP progression for CA patients. PATIENT SUMMARY: ETS-related gene (ERG) typing of tumors may be useful in prognosticating prostate cancer aggressiveness.