ERG Protein IHC Expression as an Alternative Methodology for Evaluation of ERG Fusion Status in Prostate Adenocarcinoma.
George J Netto, Roula Albadine, Alcides Chaux, Antoun Toubaji, Jessica Hicks, Alan Meeker, Angelo M Demarzo. Johns Hopkins Medical Institution, baltimore
Background: We previously demonstrated the presence of TMPRSS2-ERG gene fusions in 46% of prostatic adenocarcinomas in a large cohort, using a break-apart fluorescence in situ hybridization (FISH) technique. In the current study, we assess expression of ERG fusion protein product using immumonhistochemistry (IHC) and correlate it with our previous FISH findings in the same cohort.
Design: The cohort consisted of 10 TMAs containing paired tumor and normal tissues from radical prostatectomies (RRP) performed at our hospital between 1993 and 2001. They included 441 cases. IHC was performed using a commercial rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA), FISH analysis was previously performed using break-apart probes for 5' and 3' regions of ERG (Albadine, et al 2009). An IHC score (H score =intensity X percentage of positives cells) was assigned in each spot and averaged per tumor spots. When comparing fusion status by FISH and IHC techniques, any positive ERG expression on IHC was considered positive.
Results: ERG protein immunoexpression was detected in 202/441/ (46%) PCa and none of the paired benign prostate samples.
|No. cases||ERG =0 (%)||ERG>0 (%)||P value|
|Fusion by ERG split||<0.00001|
|Absent||327||219 (67.0)||108 (33.0)|
|Present||114||18 (15.8)||96 (84.2)|
|Fusion by ERG deletion||<0.00001|
|Absent||271||215 (79.3)||56 (20.7)|
|Present||170||22 (12.9)||148 (87.1)|
|Absent||239||211 (88.3)||28 (11.7)|
|Present||202||26 (12.9)||176 (87.1)|