TMPRSS2-ERG fusion

Moreover, two clinical trials of neoadjuvant AR inhibition prior to radical prostatectomy showed greater increases in AKT activation in the T:E fusion-positive versus -negative tumors. These findings indicate that AKT activation may mitigate the efficacy of AR-targeted therapy in T:E fusion PCa and that these patients may most benefit from combination therapy targeting AR and AKT.

High level expression of GR is strongly linked to prostate cancer aggressiveness in uni- and multivariate analysis. GR immunohistochemistry - alone or in combination with other markers - holds great potential to identify patients with a high risk for tumor progression.

The divergent molecular landscapes of EO-PC and LO-PC necessitate a fundamental shift from a standard approach to an age-aware precision medicine framework. This review highlights key therapeutic targets and underscores the critical need for a new paradigm in PC management to improve patient outcomes.

PROX1 expression is significantly associated with ERG expression and TMPRSS2-ERG fusion status in prostate cancer. These findings reinforce the role of PROX1 as an early marker and potential mediator of lineage plasticity. Targeting PROX1 or its regulatory pathways may offer a novel therapeutic strategy to mitigate plasticity-driven progression and treatment resistance in TMPRSS2-ERG fusion-positive prostate cancer.

To our knowledge, this is the first report that comprehensively evaluated the clonal origin of the rare prostate carcinosarcoma and characterized it using genomic and transcriptomic sequencing. It enhances our understanding of prostate cancer lineage plasticity and highlights the importance of developing novel therapies specifically targeted at prostate carcinosarcoma.

NGS on cytology material showed diagnostic and therapeutic utility in a subset of patients, with 10 of 46 patients (22%) having a change or potential in therapy based on NGS results.

ERG expression assessed by IHC was not associated with clinical outcomes in this population. These results do not support its role as a predictive biomarker in patients treated with CAB and RT. Further prospective studies are warranted to confirm these findings.

Moreover, in a neoadjuvant trial of AR inhibition prior to radical prostatectomy we similarly found greater increases in AKT activation in the T:E fusion tumors. Together these findings indicate that AKT activation may mitigate the efficacy of AR targeted therapy in T:E fusion PCa, and that these patients may most benefit from combination therapy targeting AR and AKT.

Incorporating multiple biomarkers, including the fPSA/tPSA ratio, PHI, PCA3, and TMPRSS2-ERG, presents a more accurate and patient-friendly approach to diagnosing PSA gray-zone prostate cancer.This multi-marker strategy enhances diagnostic precision, reduces biopsy rates, and supports the early detection of aggressive disease forms, representing a significant step forward in prostate cancer management and prognosis.

(1) PCP4 gene loss occurs at high frequency in PCa patients, and decreased expression of PCP4 correlates with poor prognosis of PCa, particularly CRPC development; (2) TMPRSS2-ERG fusion frequently co-occurs with PCP4 deletion; (3) PCP4 suppresses prostate cancer progression in vitro and in vivo; (4) PCP4 is an androgen receptor (AR) suppressed gene; (5) PCP4 was involved in the stabilization of CAMKK2 protein; (6) PCP4 inhibits PCa progression by regulating Ca2+/CAMKK2/AMPK/AR signaling axis. Our findings elucidate the molecular mechanism that PCP4 downregulation promotes PCa progression via Ca2+/CAMKK2/AMPK/AR pathway, highlighting its significance in CRPC development.

This case provides independent evidence for identification of IDH1 mutant prostate cancer by combined histologic features, including intratumoral psammomatous calcifications, anterior tumor location, and high Gleason score. In addition, to our knowledge, this is the first case of multifocal prostate cancer reported in the literature, with the co-existence of spatially disparate and genetically distinct tumor foci harboring IDH1 R132H mutation or TMPRSS2-ERG gene fusion in the same prostate.

Our proposed method significantly improves the feasibility of testing novel initiators of the T:E gene fusion and can be applied to additional studies investigating mechanisms of gene fusion initiation in prostate and other cancers.