ERG Protein Expression in Prostatic Small Cell Carcinoma Cases with Known ERG Gene Rearrangement Status.
Tamara Lotan, Alcides Chaux, Wenle Wang, Nilesh Gupta, Jonathan Epstein, Angelo De Marzo, George Netto. Johns Hopkins University School of Medicine, Baltimore, MD
Background: ERG gene rearrangements occur frequently in prostatic carcinoma and are specific to this tumor type. Previously, we showed that ERG gene rearrangements occur in nearly half of all prostatic small cell carcinoma (SCC) cases making ERG rearrangement a promising marker of prostatic origin in this tumor type. Here, we looked at ERG protein expression by immunohistochemistry (IHC) in prostatic SCC and associated acinar carcinoma (ACa) with known ERG gene rearrangement status.
Design: IHC for ERG was performed on a TMA constructed from 30 cases of prostatic SCC. Fluorescence in situ hybridization (FISH) was performed on the same TMA using a break-apart probe for 5' and 3' ERG. Cases were scored for nuclear ERG protein expression and a case was considered to express ERG protein if greater than 10% of cells expressed ERG at a 1+ or greater intensity. Cases were scored for the presence or absence of ERG gene rearrangement through deletion or translocation in at least 50 cells.
Results: Overall, 20% of prostatic SCC cases (6/30) expressed ERG protein by IHC. FISH results for ERG gene rearrangement were available in 73% of SCC cases (22/30). Of the cases with known ERG rearrangement by FISH, 40% (4/10) were positive for ERG protein by IHC. The specificity of ERG IHC for gene rearrangement was high, with 92% of cases (11/12) that were negative for rearrangement also negative for ERG protein expression. Similarly, all normal prostate epithelium adjacent to SCC tumors spotted on the TMA was negative for ERG protein (6/6 cases). The sensitivity of ERG IHC for ERG gene rearrangement was considerably higher in the concurrent ACa tumors. 27% of SCC cases (6/22) had a concurrent ACa tumor component present on the array with evaluable FISH results. Of these, 67% (4/6) had ERG gene rearrangement present and 100% of these cases (4/4) were positive for ERG protein by IHC. Interestingly, 50% of cases (2/4) with ERG rearrangement in both the ACa and SCC components were negative for ERG protein expression in the SCC component and positive for ERG protein in the concurrent ACa component.
Conclusions: The sensitivity of ERG IHC for ERG gene rearrangement is relatively low in prostatic SCC. The lack of ERG protein expression in more than half of SCC cases with known ERG gene rearrangement may be in part due to the fact that this tumor type is often androgen-insensitive. Finally, the high specificity of ERG IHC for ERG gene rearrangement makes ERG IHC a promising marker for establishing prostatic origin in SCC cases of unknown primary.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 150, Monday Afternoon