Prostate Cancer Cells with TMPRSS2-ERG Gene Fusion or ERG Overexpression Are Not Selected in the Metastatic Process
Achim Fleischmann, Outi Saramaki, Tapio Visakorpi, Inti Zlobec, George N Thalmann. University of Bern, Bern, Switzerland; University of Tampere, Tampere, Finland
Background: Prostate cancer cells with TMPRSS2-ERG gene fusion have been suggested to be selected in the metastatic process and, therefore, to indicate aggressive tumors.
Design: TMPRSS2-ERG gene fusion status and ERG protein expression were determined by fluorescence in-situ hybridization and immunohistochemistry on a tissue-microarray constructed from 119 hormone-naïve prostate cancers having lymph node metastases and being treated by radical prostatectomy and extended pelvic lymphadenectomy. Data were correlated with tumor features (Gleason score, stage, cancer volume, nodal tumor burden) and survival.
Results: TMPRSS2-ERG fusion status and ERG protein expression were highly concordant (98%) in spot-by-spot comparison; however, fusion positive samples showed some variation in immunohistochemical staining intensities. TMPRSS2-ERG fusion was detected in 43.5% of the primary tumors and in 29.9% of the metastasizing components. Concordance in TMPRSS2-ERG status between primary tumors and metastases was poor (Kappa 0.39); 22.1% of the patients showed the fusion in both tumor components, 48.9% were fusion-negative and 20.9% and 8.1% of the patients showed the mutation solely in their primary tumors and metastases, respectively. TMPRSS2-ERG fusion was not correlated with histopathological tumor features but predicted late biochemical recurrence independently when present in the primary tumor (HR 0.65; p=0.041). The better disease specific and overall survival of these patients missed to add independent prognostic information (p=0.071 and p= 0.092). Fusion status in the metastases was no prognosticator.
Conclusions: TMPRSS2-ERG fusion positive and ERG overexpressing cells are not selected in the metastatic process. Presence of the gene fusion in primary tumors predicts favorable outcome.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 177, Tuesday Afternoon