ERG Protein Expression and Genomic Rearrangement Status in Primary and Metastatic Prostate Cancer – A Comparative Study of Two Monoclonal Antibodies
Martin Braun, Diane Goltz, Zaki Shaikibrahim, Wenzel Vogel, Diana Boehm, Veit Scheble, Albert Dobi, Falko Fend, Nicolas Wernert, Glen Kristiansen, Sven Perner. University Hospital of Bonn, Bonn, Germany; University Hospital of Tuebingen, Tuebingen, Germany; Uniformed Services University of the Health Sciences, Rockville
Background: Overexpression of the ERG protein is highly prevalent in prostate cancer (PCa) and most commonly results from gene fusions involving the ERG gene. Recently, an N-terminal epitope targeted mouse and a C-terminal epitope targeted rabbit monoclonal anti-ERG antibody have been introduced for the detection of the ERG protein. Independent studies reported that immunohistochemical (IHC) stains with both monoclonal anti-ERG antibodies (ERG-MAbs) highly correlate with the underlying ERG gene rearrangement status. However, a comparative study of both antibodies has not been provided so far. Here, we are the first to compare the mouse ERG-MAb to the rabbit ERG-MAb for their concordance on the same PCa cohort. Furthermore, we assessed if the ERG protein expression is conserved in lymph node and distant PCa metastases, of which a subset underwent decalcification.
Design: We evaluated tissue microarrays of 278 specimens containing 265 localized PCa, 29 lymph node, 30 distant metastases, and 13 normal prostatic tissues. We correlated the ERG protein expression with the ERG rearrangement status using an ERG break-apart fluorescence in-situ hybridization (FISH) assay and IHC of both ERG antibodies.
Results: ERG protein 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. If an ERG protein expression was present in localized PCa, we observed the same pattern in the corresponding lymph node metastases.
Conclusions: This is the first study to comprehensively compare the two available ERG-MAbs. By demonstrating a broad applicability of IHC to study ERG protein expression using either antibody, this study adds an important step towards a facilitated routine clinical application. Further, we demonstrate that the clonal nature of the ERG rearrangement is not restricted the genomic level, but proceeds in the proteom. Together, our results simplify future efforts to further eliucidate the biological role of ERG in PCa.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 172, Monday Afternoon