TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications

Abstract

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.

Figure 1. Representative example of a heterogeneous case (Case #9) and a summary of the results for all cases

A–C: H&E sections from the anterior half of prostate with two spatially separate foci of cancer showing no fusion (A and B) and fusion by insertion (A and C). The insert in B shows a nucleus with two yellow signals (juxtaposed red and green signals) indicating that there is no fusion. The insert in C shows one yellow signal and split red and green signals, indicating that fusion through insertion has taken place. D: Piechart summary of the results of the study with cases showing interfocal homogeneity in light grey (fusion) and dark grey (no fusion) and cases showing interfocal heterogeneity in light red (fusion and no fusion) and dark red (clonally distinct fusion).