ERG rearrangement metastasis patterns in locally advanced prostate cancer.
OBJECTIVE
To interrogate multifocal prostate cancer (PCa) to determine its predilection for metastasis, using ERG rearrangement as marker of clonality. A hallmark of PCa is that distinct tumor foci may arise independently, which has important biological and clinical implications. Recent studies characterizing ERG-rearranged PCa possessing intrafocal homogeneity but interfocal heterogeneity support this hypothesis.


METHODS
We studied 26 patients who underwent prostatectomy and lymphadenectomy with at least 2 distinct PCa foci and 1 lymph node (LN) metastasis. Each focus was assessed for size, Gleason score, ERG rearrangement, and TMPRSS2-ERG transcript.


RESULTS
Fifteen of 26 cases exhibited interfocal homogeneity with regard to ERG rearrangement (ie, presence vs absence of ERG rearrangement). ERG rearrangement was present in all foci for 6 and absent in all foci for 9 cases. Two cases revealed interfocal heterogeneity with regard to rearrangement mechanism (ie, rearrangement through insertion or deletion). Eight of 26 cases revealed interfocal heterogeneity with regard to rearrangement status. In all cases with at least 1 ERG rearranged focus, we found the corresponding LN metastasis harboring an ERG rearrangement. Interestingly, in a subset of cases the rearrangement status in the LN did not correspond to size or Gleason score. All but 2 ERG rearranged foci had detectable TMPRSS2-ERG transcript levels.


CONCLUSIONS
When multifocal PCa demonstrates both ERG-positive and ERG-negative foci, the positive foci have a greater predilection for metastasis. Larger studies are needed to confirm the potential additional risk an ERG rearranged focus confers on the likelihood of disease progression.
Perner
Sven
S
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
Svensson
Maria A
MA
Hossain
Ruhella R
RR
Day
John R
JR
Groskopf
Jack
J
Slaughter
Ryan C
RC
Jarleborn
Analee R
AR
Hofer
Matthias D
MD
Kuefer
Rainer
R
Demichelis
Francesca
F
Rickman
David S
DS
Rubin
Mark A
MA
D000368:Aged; D015321:Gene Rearrangement; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
C072312:ERG protein, human; D015513:Oncogene Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG