ERG Rearrangement Status in Prostate Cancer Detected by Immunohistochemistry.
Sara M Falzarano, Ming Zhou, Paula Carver, Huiying He, Cristina Magi-Galluzzi. Cleveland Clinic
Background: TMPRSS2:ERG is the most common gene fusion in prostate cancer (PCA). It has been associated with expression of a truncated protein product of the oncogene ERG. A novel anti-ERG monoclonal antibody has been recently characterized which specifically recognizes all ERG gene fusion related isoforms. We investigated the correlation between ERG rearrangement assessed by fluorescence in situ hybridization (FISH) and ERG expression detected by immunohistochemistry (IHC) in a large cohort of patients from a single institution.
Design: 345 tumor foci from a cohort of 307 patients treated with radical prostatectomy for clinically localized PCA were included in the study. 13 tissue microarrays (TMAs) comprising all tumors and a subset of non neoplastic tissue samples were assessed for ERG rearrangement status by FISH and ERG expression by IHC. The accuracy of ERG detection by IHC in predicting ERG status as assessed by FISH (gold standard) was calculated in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).
Results: 305 (88%) tumor samples were informative for both FISH and IHC. 40 cases were not evaluable by either FISH (34) or IHC (6). Of the 103 (34%) ERG rearranged cases, 49 (47%) were positive by deletion, 47 (46%) by translocation and 7 (7%) by both mechanisms. ERG detection by IHC demonstrated a sensitivity and specificity of 96% and 99%, respectively, with a PPV of 99% and a NPV of 98% (Table 1). We identified 1 case with positive ERG expression and no identifiable ERG rearrangement by FISH and 4 rearranged cases with no expression of ERG. None of the 112 informative non neoplastic tissue samples was rearranged by FISH or showed any ERG expression.
Conclusions: ERG detection by IHC in PCA was highly predictive of ERG rearrangement as assessed by FISH in a large cohort of RP patients. Given the high yield and the easier task of performing IHC vs. FISH, ERG assessment by IHC may be useful for characterizing ERG status in PCA. Although a rare event (4%), the inefficient transcription/translation of the gene fusion product may be responsible for cases with gene rearrangement by FISH which do not express ERG, whereas ERG synthesis and overexpression may occur in absence of gene rearrangement detected by the FISH break-apart system.
|FISH Positive||FISH Negative||Total|
|IHC Positive||99 (32%)||1 (0%)||100 (33%)|
|IHC Negative||4 (1%)||201 (66%)||205 (67%)|
|Total||103 (34%)||202 (66%)||305 (100%)|