OBJECTIVE
Tosystematically evaluate ERG alterations in the multifocal tumor context by using whole-mount prostatectomy specimens of African American and Caucasian American patients matched for age, pathologic grade and stage. Oncogenic activation of the ETS-Related Gene (ERG) is the most common early genomic alteration in prostate cancer patients in Western countries. However, ERG alterations have not been systematically examined in African American patients with known higher risk of prostate cancer incidence and mortality.
METHODS
ERG oncoprotein expression was analyzed in 91 Caucasian American and 91 African American prostate cancer patients matched for age, Gleason score and pathologic stage. A unique aspect of this study was the evaluation of ERG in whole-mount prostatectomy sections, minimizing sampling bias and allowing the careful assessment of ERG in the multifocal tumor context of prostate cancer.
RESULTS
The frequency of ERG positive prostate tumors was significantly greater among Caucasian Americans vs. African Americans when assessed in all tumor foci (41.9% vs. 23.9%, p<0.0001). Markedly higher frequency of the ERG oncoprotein expression was noted between the index tumors of Caucasian Americans (63.3%) and African Americans (28.6%). Of note, in African American patients the higher grade index tumors were predominantly ERG negative.
CONCLUSIONS
ERG typing of prostate tumors establishes a major difference between the index tumors of Caucasian and African American patients. ERG negative index tumors may indicate less favorable outcome in African American patients. This study underscores that typing of prostate tumors for ERG may enhance our understanding of biological differences between the examined ethnic groups.
The administration of suramin was simplified and the drug concentrations were maintained. In this cohort of patients with advanced prostate cancer, the clinical activity of suramin using these dosing schedules was limited. Pharmacodynamic issues, patients selection, and criteria to assess efficacy could have effected the clinical outcome.
Introduction and Objective: The ETS-related gene (ERG) proto-oncogene is frequently overexpressed in prostate cancer (CaP) as a result of a genomic rearrangement that places ERG under the control of the androgendependent TMPRSS2 promoter. The initial report of quantitative ERG mRNA expression in micro-dissected prostate tumor cells showed significantly higher ERG expression in CaP of Caucasian-Americans (CA) patients vs. African-American (AA) patients (Petrovics et al, Oncogene, 2005). Recent studies (Magi-Galluzzi et al, Prostate, 2011; Elliott et al, USCAP Mtg., 2011) have also shown higher frequency of ERG rearrangement or ERG oncoprotein expression in CaP of CA patients. We evaluate the frequency and pattern of the ERG oncoprotein expression in prostate tumors of matched CA and AA CaP patients to better understand the biological basis for differences in prostate cancer between the two populations.
Methods: Ninety one AA and 91 CA CaP patients were matched for age, Gleason score and pathologic stage. All underwent radical prostatectomy between 1993 and 2010. Whole mount prostate specimens were used for the immunohistochemical detection of the ERG oncoprotein by a highly specific ERG monoclonal antibody (clone 9FY). Individual foci of tumors were reported as either positive or negative. ERG staining data was linked to clinico-pathologic data. Biochemical recurrence was defined as two serum PSA measurements of 0.2 ng/mL or higher at least 8 weeks from surgery.
Results: A higher percentage of CA (61.8%) than AA (28.2%) CaP patients had ERG positive index tumors and had at least one focus of tumor positive for ERG. A higher percentage of overall tumor foci were also positive for ERG in CA than AA CaP patients. There was high concordance of ERG positive prostatic intra-epitheilal neoplasia (PIN) and ERG positive CaP in both AA and CA patients.
Conclusions: ERG expression is more prevalent among CA than AA CaP patients in matched cohorts. Differences in the pattern of ERG expression in CaP and differing trends in biochemical recurrence between CA and AA patients with ERG (+) index tumors suggest a dominant clonal selection of ERG-positive tumors in CA patients. These differences in ERG expression have the potential to delineate biological distinctions of CaP in the two patient populations.
Citation Format: Gyorgy Petrovics, Philip Rosen, David Pfister, Denise Young, Yongmei Chen, Albert Dobi, David McLeod, Shiv Srivastava, Isabell Sesterhenn. Distinguishing features of ERG oncoprotein expression among matched cohorts of African-American and Caucasian-American prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A29.
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