Prevalence and clinical application of TMPRSS2-ERG fusion in Asian prostate cancer patients: A large-sample study in Chinese people and a systematic review / 亚洲男科学杂志(英文版)

Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG fusion) is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer. However, the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups, and contradictory results have been reported in Asian patients. We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians. We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China. We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan-Meier analysis. Finally, a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients. McNemar's test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods. The positive rates of TMPRSS2-ERG fusion were 16% in our samples and 27% in Asian patients. In our samples, 9.4% and 19.3% of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry, respectively. No significant association between the fusion and clinical parameters was observed. TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China. Besides ethnic difference, detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.

Progress on TMPRSS2-ERG fusion gene product transcription regulation mechanism in prostate cancer cells / 中国临床药理学与治疗学

Prostate cancer is the most common malignant tumor in men in Europe and the United States, but the mechanism of prostate cancer occurrence and development is not completely clear. In prostate cancer, the TMPRSS2-ERG fusion gene has a high incidence, which promotes ERG overexpression and causes changes in target genes and signaling pathways, such as androgen receptors, spotted zinc finger structural proteins, Notch pathways. In-depth understanding of the transcriptional regulation mechanism of TMPRSS2-ERG fusion gene products in prostate cancer cells can provide new targets for drug action in the treatment of prostate cancer.

Prevalence and clinical application of TMPRSS2-ERG fusion in Asian prostate cancer patients: a large-sample study in Chinese people and a systematic review / 亚洲男科学杂志(英文版)

Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG fusion) is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer. However, the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups, and contradictory results have been reported in Asian patients. We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians. We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China. We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan-Meier analysis. Finally, a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients. McNemar's test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods. The positive rates of TMPRSS2-ERG fusion were 16% in our samples and 27% in Asian patients. In our samples, 9.4% and 19.3% of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry, respectively. No significant association between the fusion and clinical parameters was observed. TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China. Besides ethnic difference, detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.

Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate

@#Introduction: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. Methods: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. Results: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). Conclusion: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity. @*@#

Preliminary Results of Noninvasive Detection of TMPRSS2:ERG Gene Fusion in a Cohort of Patients With Localized Prostate Cancer

PURPOSE: The aim of this study was to evaluate TMPRSS2:ERG fusion rates in tissue, urine, blood, and pubic hair samples in a cohort of patients with localized prostate cancer and to correlate these findings with various clinicopathological parameters. MATERIALS AND METHODS: A cohort of 40 patients undergoing radical prostatectomy for localized prostate cancer (RRP group) and 10 control patients undergoing prostate biopsy were enrolled between 2006 and 2008. Urine, pubic hair, and peripheral blood samples were obtained following prostatic massage before the needle biopsy or radical prostatectomy. Quantitative polymerase chain reaction analysis was performed on all collected samples. RESULTS: The patients' mean age was 62.4 (+/-5.5) years. We observed higher expressions of TMPRSS2:ERG fusion in tissue, urine, and blood samples from the RRP group than in samples from the control group. Overall, the fusion was present in urine samples of 23 RRP patients (57.5%). To predict high-stage cancer (>T3a), the Gleason score was the only significant factor in the logistic regression analysis (score, 10.579; p=0.001). Quantitative evaluation of the gene fusion in tissue (Pearson r=0.36, p=0.011) and urine (Pearson r=0.34, p=0.014) samples had a significant positive correlation with the preoperative prostate-specific antigen level. CONCLUSIONS: Urine sediments collected after prostatic massage appear to be a feasible noninvasive method of detecting TMPRSS2:ERG fusion. The Gleason score is the only significant factor to predict high-stage cancer (>T3a). No correlation between TMPRSS2:ERG gene fusion status and tumor stage, Gleason grade, prostate-specific antigen level, or surgical margin status was observed.