ERG Protein Expression and Genomic Rearrangement Status in Primary and Metastatic Prostate Cancer--a Comparative Study of Two Monoclonal Antibodies

Background: Overexpression of the ERG protein is highly prevalent in prostate cancer (PCa) and commonly results from gene fusions involving the ERG gene. Recently, N-terminal epitope-targeted mouse and a C-terminal epitope-targeted rabbit monoclonal anti-ERG antibody (ERG-MAbs) have been introduced for the detection of the ERG protein. Independent studies reported that immunohistochemistry (IHC) with both ERG-MAbs highly correlates with the underlying ERG gene rearrangement status. However, comparative studies of both antibodies are lacking. Here, we are among the first to compare the mouse ERG-MAb with the rabbit ERG-MAb for their concordance on the same PCa cohort. Furthermore, we assessed whether the ERG protein expression is conserved in lymph node and distant PCa metastases.

Methods: We evaluated tissue microarrays of 278 specimens containing 265 localized PCa, 29 lymph node, 30 distant metastases and 13 normal prostatic tissues. We correlated ERG protein expression with ERG rearrangement status using an ERG break-apart fluorescence in-situ hybridization assay and IHC of both ERG-MAbs.

Results: ERG expression and ERG rearrangement status were highly concordant regardless of whether the mouse or rabbit ERG-MAb was used (97.8% versus 98.6%, respectively). Of interest, both ERG antibodies reliably detected the ERG expression in lymph node and distant PCa metastases, of which a subset underwent decalcification. Lymphocytes only revealed immunoreactivity using the rabbit ERG-MAb. If ERG protein expression was present in localized PCa, we observed the same pattern in the corresponding lymph node metastases.

Conclusions: By demonstrating a broad applicability of IHC to study ERG protein expression using either antibody, this study adds an important step toward a facilitated routine clinical application. Further, we demonstrate that the clonal nature of the ERG rearrangement is not restricted to the genomic level, but proceeds in the proteome. Together, our results simplify future efforts to further eliucidate the biological role of ERG in PCa.