<i>TMPRSS2:ERG</i> status was assessed by IHC for presence of ERG on archival tumor specimens for 912 patients with prostate cancer, of whom 48% were ERG-positive.<b>Results:</b> In multivariable models, we found no association between regular use of aspirin and risk of <i>ERG</i>-positive prostate cancer (HR, 1.02; 95% confidence interval, 0.85-1.23), nor any association with duration or frequency of aspirin use.
PCA3 and TMPRSS2:ERG had additional independent predictive value for the prediction of PCa detection and progression, although PCA3 was limited in predicting aggressive cancer.
The purpose of this study was to first investigate the expression of seven different PC-related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9.
Harboring the TMPRSS2:ERG fusion was associated with a statistically significant lower risk of prostate cancer mortality among men who were treated with orchiectomy (multivariable HR: 0.13; 95% CI: 0.03-0.62), based on 15 events.
Samples from 134 patients diagnosed with prostate cancer (84 local recurrent castration resistant prostate cancer, 55 distant metastatic prostate cancer) were assessed for their ERG rearrangement and AR amplification status by fluorescence in situ hybridization.
TMPRSS2 gene fusions with ETS transcription factor family members ERG, ETV1, or ETV4 have been recently discovered as a common molecular event in prostate cancer.
First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG.
In our series of patients with prostate cancer over expression of the ERG gene predicted the presence of TMPRSS2-ERG rearrangements in almost all cases.
Moreover, TMPRSS2-ERG affects the pattern of metastatic spread by increasing the incidence of tumors in hind limbs and spine, which are two of the most frequent sites of human PCa metastases.
Kaplan-Meir plots and long rank tests were used to assess the association of ERG and PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer.
Recurrent deletion of 3p13 targets multiple tumour suppressor genes and defines a distinct subgroup of aggressive ERG fusion-positive prostate cancers.
In this review, we will summarize the histologic features of known recurrent genomic rearrangements in carcinomas, especially focusing on TMPRSS2-ERG fusion in prostate cancer, EML4-ALK in lung cancer, ETV6-NTRK3 in secretory breast cancer, RET/PTC and PAX8/PPARγ1 rearrangements in thyroid cancer.
While these alterations seem to be independent of copy number alterations in the PDE4D locus and driven by AR and ERG binding, we also observed increased DNA methylation in the promoter region of PDE4D5, indicating a long lasting alteration of the isoform composition in prostate cancer tissues.We propose two independent metrics that may serve as diagnostic and prognostic markers for prostate disease: (PDE4D7 - PDE4D5) provides an effective means for distinguishing PCa from normal adjacent prostate, whereas PDE4D1/2 - (PDE4D5 + PDE4D7 + PDE4D9) offers strong prognostic potential to detect aggressive forms of PCa and is associated with metastasis free survival.
Finally, the development of molecular biology has opened the study of genes, among them TMPRSS2:ERG fusion gene and miRNAs, in PCa detection and prognosis.
Immunohistochemistry demonstrated a reciprocal relationship of ANXA2 and ERG expression in a large fraction of primary prostate cancer clinical specimens.