[903] 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.

ERG expression by IHC vs ERG fusion by FISH in large cohort of prostatic adenocarcinoma

	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)
ERG fusion				<0.00001
Absent	239	211 (88.3)	28 (11.7)
Present	202	26 (12.9)	176 (87.1)

Conclusions: We were able to demonstrate ERG fusion protein expression in 46% of prostate adenocarcinoma using EPR 3864 monoclonal anti-ERG antibody. A strong correlation between ERG rearrangement status by FISH and positive IHC expression of ERG fusion protein product is demonstrated. ERG protein IHC expression may offer an accurate alternative for evaluation of ERG fusion status in PCa. The significance and underlying mechanisms of our finding of a subset of tumors with discrepant ERG protein expression /TMPRSS2-ERG fusion status (IHC positive/FISH negative) warrants further investigation.
Category: Genitourinary (including renal tumors)

Monday, February 28, 2011 1:00 PM

Poster Session II # 98, Monday Afternoon