TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications.
OBJECTIVE
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.
Barry
Marc
M
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Perner
Sven
S
Demichelis
Francesca
F
Rubin
Mark A
MA
D001707:Biopsy, Needle; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000652:urine; D050939:Gene Fusion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics* / Q000652:urine; D015534:Trans-Activators / Q000235:genetics* / Q000652:urine; D000071230:Transcriptional Regulator ERG
D004268:DNA-Binding Proteins; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human