Related Experiment Video
Updated: Jul 10, 2026
A Cognitive Fusion-guided Prostate Biopsy Using Multiparametric Magnetic Resonance Imaging and Transrectal Ultrasound
Published on: March 21, 2025
TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications
Marc Barry1, Sven Perner, Francesca Demichelis
1Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Objectives:
To characterize the clonality of TMPRSS2-ERG fusion in multifocal prostate cancer.
Methods:
From 80 consecutive radical prostatectomy specimens, we identified 32 cases with multiple spatially separate tumors. In each case, we assessed two to three tumor foci for TMPRSS2-ERG fusion using an ERG break-apart interphase fluorescence in situ hybridization assay.
Results:
Individual tumor foci showed homogeneity for fusion status (intrafocal clonal homogeneity). In 19 (59%) of the 32 cases, all foci within a case had the same fusion status (interfocal homogeneity). In 15 (80%) of the 19 cases, no foci had fusion, and in 4 (20%), all foci had fusion. Of the 32 cases, 13 (41%) demonstrated heterogeneity for fusion status within a case (interfocal clonal heterogeneity).
Conclusions:
In this study, we have demonstrated interfocal heterogeneity and intrafocal homogeneity for TMPRSS2-ERG fusion in prostate cancer with multiple tumors. These findings support the multiclonal nature of prostate cancer with clinical implications for needle biopsy strategies and the development of urine-based screening tests.
Insights
Prostate cancer with multiple tumors often shows different TMPRSS2-ERG fusion statuses within a single patient, indicating a multiclonal origin. This heterogeneity impacts diagnostic strategies and screening test development.
Area of Science:
- Urologic Oncology
- Cancer Genetics
- Molecular Pathology
Background:
- Multifocal prostate cancer presents a clinical challenge due to potential intra-patient tumor heterogeneity.
- The TMPRSS2-ERG fusion is a common genetic alteration in prostate cancer, but its clonal behavior in multifocal disease is not fully understood.
Purpose of the Study:
- To investigate the clonality of TMPRSS2-ERG fusion across multiple tumor foci in patients with multifocal prostate cancer.
- To determine the extent of interfocal and intrafocal homogeneity or heterogeneity for this fusion gene.
Main Methods:
- Analysis of 32 radical prostatectomy specimens with spatially distinct tumors.
- Assessment of TMPRSS2-ERG fusion status in 2-3 tumor foci per case using ERG break-apart fluorescence in situ hybridization (FISH).
Main Results:
- Intrafocal homogeneity for TMPRSS2-ERG fusion status was observed within individual tumor foci.
- Interfocal heterogeneity was found in 41% of cases, with different fusion statuses across tumor foci.
- Interfocal homogeneity was present in 59% of cases, where all foci shared the same fusion status (either fusion-positive or fusion-negative).
Conclusions:
- Prostate cancer with multiple tumors exhibits interfocal heterogeneity and intrafocal homogeneity for TMPRSS2-ERG fusion.
- These findings support a multiclonal model for prostate cancer development.
- Understanding this heterogeneity has implications for improving needle biopsy accuracy and developing novel urine-based screening tests.
