Past, Current, and Future Strategies to Target ERG Fusion-Positive Prostate Cancer

Lorenzin, Francesca; Demichelis, Francesca

doi:10.3390/cancers14051118

Cited by 11 publications

(12 citation statements)

References 204 publications

(266 reference statements)

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“…Although the results of clinical studies on the prognostic value of ERG fusion detection in prostate cancer patients remain unclear, its potential as diagnostic biomarker is evident as it is specific for prostate cancer [3].…”

Section: Discussionmentioning

confidence: 99%

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The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples

Feitosa

Hirth

Silva-Fernandes

et al. 2023

APMIS

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Prostate cancer is the world's most frequently diagnosed malignancy in men. Recent work suggests that patients with high ERG expression intensity are significantly more likely to develop biochemical relapse and metastasis, and die of prostate cancer. The objective of this study was to determine the relationship between the intensity of ERG protein expression and the staging of prostate cancer and the formation of metastases in 635 samples. A retrospective cohort analysis was performed using immunohistochemistry reactions in tissue microarray samples taken from non‐neoplastic and neoplastic prostate tissue from patients who underwent radical prostatectomies at a reference hospital from 2009 to 2016. For the ERG marker analysis, the samples were scored for the presence or absence of nuclear signals. Weak, moderate, or strong intensity of the nuclei of the observable tumor cells was considered to be positive markers. All told, 635 samples were evaluated, and the ERG expression was inconclusive in 9% of cases, while 30% were positive and 61% were negative. Of the samples with positive result: 25.8% were weak and focal, 53.2% were moderate, and 21% were strong. Finally, 21% of the cases with a positive ERG had a high Gleason score. Metastasis was detected in 41% of the patients who were ERG positive, and of these, the majority had moderate marking and were aged older than 60 years, although there was no statistically significant difference between the older and younger age groups. Patients with moderate to strong ERG staining had higher staging compared to the others, and no increase in metastasis was detected in patients with more intense ERG expression. More studies should be carried out to corroborate these results and to reach a consensus on the intensity and scoring of the expression levels of ERG markers.

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Section: Discussionmentioning

confidence: 99%

“…ERG plays a central role in prostate cancer [3,4]. Associations between the intensity of ERG protein expression and clinicopathological parameters, including prostate cancer staging and metastasis formation, have varied between studies.…”

Section: Introductionmentioning

confidence: 99%

The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples

Feitosa

Hirth

Silva-Fernandes

et al. 2023

APMIS

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“…However, large-scale studies are needed to identify the role of T2:ERG in real-world clinical practice and its role as a possible target for a future new targeted therapy strategy ( 42 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

“…With the development of precision medicine, the association of T2:ERG with germline mutations is arousing more and more interest: in the era of selective and targeted medicine with dedicated screening pathways, PCa management should include specific machine learning algorithms implemented with the detection of specific gene mutations (43, 44). However, large-scale studies are needed to identify the role of T2:ERG in real-world clinical practice and its role as a possible target for a future new targeted therapy strategy (42,45).…”

Section: Discussionmentioning

confidence: 99%

Prospective evaluation of the role of imaging techniques and TMPRSS2:ERG mutation for the diagnosis of clinically significant prostate cancer

et al. 2022

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ObjectivesTo test the hypothesis of a relationship between a specific genetic lesion (T2:ERG) and imaging scores, such as PI-RADS and PRI-MUS, and to test the effectiveness of these parameters for the diagnosis of prostate cancer (PCa) and clinically significant PCa (csPCa).Materials and methodsThis is a prospective study of men with suspected PCa enrolled between 2016 and 2019 at a high-volume tertiary hospital. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they were presenting with >=1 suspicious lesion (PI-RADS>2) at mpMRI or PR-IMUS >2 at micro-ultrasound assessment. For each patient, one core from the highest PI-RADS or PRI-MUS lesion was collected for T2:ERG analysis. Multivariable logistic regression models (LRMs) were fitted for csPCa with a clinical model (age, total PSA, previous biopsy, family history for PCa), a clinical plus PI-RADS, clinical plus T2:ERG, clinical plus PI-RADS plus T2:ERG, and T2:ERG plus PI-RADS alone.ResultsThe cohort consists of 158 patients: 83.5% and 66.2% had respectively a diagnosis of PCa and csPCa after biopsy. A T2:ERG fusion was found in 37 men and 97.3% of these patients harbored PCa, while 81.1% were diagnosed with csPCa. SE of T2:ERG assay for csPCa was 28.8%, SP 87.0%, NPV 38.8%, and PPV 81.1%. Of 105 patients who performed mpMRI 93.% had PIRADS ≥3. SE of mpMRI for csPCa was 98.5%, SP was 12.8%, NPV was 83.3%, and PPV was 65.7%. Among 67 patients who were subjected to micro-US, 90% had a PRI-MUS ≥3. SE of micro-US for csPCa was 89.1%, SP was 9.52%, NPV was 28.6%, and PPV was 68.3%. At univariable LRM T2:ERG was confirmed as independent of mpMRI and micro-US result (OR 1.49, p=0.133 and OR 1.82, p=0.592, respectively). At multivariable LRM the clinical model alone had an AUC for csPCa of 0.74 while the clinical model including PI-RADS and T2:ERG achieved an AUC of 0.83.ConclusionsT2:ERG translocation and imaging results are independent of each other, but both are related csPCa. To evaluate the best diagnostic work-up for PCa and csPCa detection, all available tools (T2:ERG detection and imaging techniques) should be employed together as they appear to have a complementary role.

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“…The ETS family is characterized by a common ETS DNA‐binding domain with a helix‐turn‐helix motif, which is essential for DNA recognition and binding, and thus their role as transcription factors [12]. ERG and other ETS factors are involved in a variety of normal physiological processes, for example, angiogenesis and vascular homeostasis, through regulation of genes specific to endothelial cells ( e.g ., VE‐cadherin) and the Wnt/β‐catenin pathway [10,13]. In cancer, oncogenic ETS proteins, including ERG , ETV1 , and ETV4 , have been found to bind a common set of genomic regions that potentially regulate processes such as differentiation, proliferation, and angiogenesis [14].…”

Section: Introductionmentioning

confidence: 99%

In situ expression of ERG protein in the context of tumor heterogeneity identifies prostate cancer patients with inferior prognosis

Bogaard

Carm

et al. 2022

Molecular Oncology

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Prognostic biomarkers for prostate cancer are needed to improve prediction of disease course and guide treatment decisions. However, biomarker development is complicated by the common multifocality and heterogeneity of the disease. We aimed to determine the prognostic value of candidate biomarkers transcriptional regulator ERG and related ETS family genes, while considering tumor heterogeneity. In a multisampled, prospective, and treatment‐naïve radical prostatectomy cohort from one tertiary center (2010–2012, median follow‐up 8.1 years), we analyzed ERG protein (480 patients; 2047 tissue cores), and RNA of several ETS genes in a subcohort (165 patients; 778 fresh‐frozen tissue samples). Intra‐ and interfocal heterogeneity was identified in 29% and 33% (ERG protein) and 39% and 27% (ETS RNA) of patients, respectively. ERG protein and ETS RNA was identified exclusively in a nonindex tumor in 31% and 32% of patients, respectively. ERG protein demonstrated independent prognostic value in predicting biochemical (P = 0.04) and clinical recurrence (P = 0.004) and appeared to have greatest prognostic value for patients with Grade Groups 4–5. In conclusion, when heterogeneity is considered, ERG protein is a robust prognostic biomarker for prostate cancer.

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Past, Current, and Future Strategies to Target ERG Fusion-Positive Prostate Cancer

Cited by 11 publications

References 204 publications

The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples

The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples

Prospective evaluation of the role of imaging techniques and TMPRSS2:ERG mutation for the diagnosis of clinically significant prostate cancer

In situ expression of ERG protein in the context of tumor heterogeneity identifies prostate cancer patients with inferior prognosis

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