The TMPRSS2-ERG fusion has been reported in 42 to 78% of prostate tumors. More than 90% of ERG-overexpressing tumors harbor the fusion. The relationship between the TMPRSS2-ERG fusion and prognosis is controversial. Different studies have suggested an association between CXCR4 and ERG overexpression resulting from the TMPRSS2-ERG rearrangement. The aim of this study was to investigate the relationship between CXCR4 expression, TMPRSS2-ERG fusion and Gleason grade in prostate cancer. TMPRSS2-ERG rearrangement was investigated by FISH (n=44), ERG protein by IHC (n=84), and CXCR4 by quantitative RT-PCR (n=44). TMPRSS2-ERG rearrangement and ERG protein expression were present in almost 50% of the cases, without statistical differences between the different Gleason score groups. There was a very high concordance between FISH and IHC techniques (Kappa Index=0.954). Seventy percent of Gleason ⩾ 8 prostate tumors overexpressed CXCR4 mRNA, and the difference in CXCR4 expression with Gleason < 8 cases was statistically significant (p=0.009). There was no association between ERG protein and CXCR4 mRNA expression. In conclusion, our results reveal for the first time that CXCR4 overexpression is associated with high Gleason score prostate tumors, but that it is independent of the TMPRSS2-ERG rearrangement.
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http://dx.doi.org/10.3233/CBM-2012-00288 | DOI Listing |
Front Biosci (Landmark Ed)
September 2024
Department of Anesthesiology, Reanimatology and Narcology, Semey Medical University, 071400 Semey, Republic of Kazakhstan.
Chromosomal rearrangements and recurrent gene fusions were previously presumed to be the primary oncogenic mechanisms of hematological malignancies. However, the discovery of gene fusions in different cancers has opened new horizons to comprehensively investigate how cell type-specific fusion oncoproteins modulate signaling cascades. Prostate cancer (PCa) is a multifaceted and therapeutically challenging disease, and functional genomics have helped us develop a better understanding of the mechanisms underlying prostate carcinogenesis, castration-resistant PCa, and metastasis.
View Article and Find Full Text PDFAnticancer Res
October 2024
Molecular Unit, Department of Pathology, Herlev Hospital, Herlev, Denmark.
Background/aim: The emergence of novel DNA damage repair (DDR) pathways in molecular-target therapy drugs (MTTD) has shown promising outcomes in treating patients with metastatic castration-resistant prostate cancer (mCRPC). About 25% of mCRPC patients have actionable deleterious aberrations in DDR genes, primarily in the homologous recombination (HR) pathway. However, the response rate in patients with BRCA1/2 or mutations in HRR-related genes is only 45%-55%, when exposed to poly ADP ribose polymerase (PARP) inhibitor-based therapy (PARPi).
View Article and Find Full Text PDFCurr Urol
June 2024
Department of Urology, York & Scarborough Teaching Hospitals NHS Foundation Trust, York, UK.
Prostate cancer (PC) is the most frequently diagnosed cancer and second leading cause of cancer-related deaths in men. It is heterogeneous, as is evident from the wide spectrum of therapeutic approaches. Most patients with PC are initially responsive to androgen deprivation therapy; however, the majority of cases are either hormone-sensitive PC or castration-resistant PC.
View Article and Find Full Text PDFNat Med
November 2024
Department of Medical Epidemiology and Biostatistics, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician's choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB).
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
December 2024
Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Purpose: TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated.
Methods: Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs.
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