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Diagnostic Technologies and Molecular and Cellular Profiling: Biomarkers in Early Detection and Diagnosis |
Uniformed Services University CPDR, Rockville, MD, Armed Forces Institute of Pathology, Washington, DC, Walter Reed Army Medical Center, Washington, DC
Abstract
A39
Introduction: ERG has been reported to be the most frequently overexpressed proto-oncogene in prostate cancer (CaP) (Petrovics et al, Oncogene, 2006) due to recurrent gene fusion (Tomlins et al, Science, 2006). To further determine diagnostic and prognostic potentials of ERG in CaP, TMPRSS2-ERG fusion and expression was analyzed in CaP patients for correlation with clinico-pathological features.Methods: Matched benign and malignant epithelial cells were obtained by laser capture micro-dissection (LCM) of radical prostatectomy (RP) specimens. RNA specimens from these cells were used for quantitative expression analyses (TaqMan RT-PCR) of ERG and TMPRSS2-ERG fusion transcripts. Patients with predominantly well differentiated (WD, N=18) and poorly differentiated (PD, N=17) tumor foci were pre-selected for analysis from a pool of over 300 CaP patients undergoing RP. Correlation with clinico-pathologic features of CaP patients was evaluated using SAS version 9.1.Results: The expression of TMPRSS2-ERG fusions, and of ERG1, was determined by QRT-PCR (normalized to GAPDH) in matched microdissected tumor and benign epithelial cells from frozen RP specimens of 112 CaP patients (224 specimens). Overall 65 (58%) of CaP patients had detectable expression of TMPRSS2-ERG fusion A transcripts in CaP cells, but not in benign prostate epithelium. However, 15 (83%) of patients with predominantly WD tumor had detectable TMPRSS2-ERG fusion A transcript in contrast to 7 (41%) of patients with substantial amount of PD tumor cells. In line with our previous observations based on ERG1 expression levels, patients with pT3-4 CaP (locally invasive tumor growing outside the capsule) had significantly lower expression of TMPRSS2-ERG fusion A transcript as compared to patients with pT2 stage disease (organ confined).Conclusions: Our study underscores both diagnostic and prognostic features of ERG and TMPRSS2-ERG gene fusion expression in CaP, and confirms that ERG fusion A is the predominant gene fusion in CaP cells. Decreased expression of TMPRSS2-ERG fusion transcript significantly associated with poor tumor differentiation status and with more advanced pathological stage of CaP.
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