ERG rearrangement metastasis patterns in locally advanced prostate cancer.

TitleERG rearrangement metastasis patterns in locally advanced prostate cancer.
Publication TypeJournal Article
Year of Publication2010
AuthorsPerner S, Svensson MA, Hossain RR, Day JR, Groskopf J, Slaughter RC, Jarleborn AR, Hofer MD, Kuefer R, Demichelis F, Rickman DS, Rubin MA
JournalUrology
Volume75
Issue4
Pagination762-7
Date Published2010 Apr
ISSN1527-9995
KeywordsAged, Gene Rearrangement, Humans, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Staging, Oncogene Proteins, Prostatic Neoplasms, Trans-Activators
Abstract

OBJECTIVES: 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.

DOI10.1016/j.urology.2009.10.010
Alternate JournalUrology
PubMed ID20018353
PubMed Central IDPMC2850965
Grant ListR01 CA116337 / CA / NCI NIH HHS / United States
R01 CA116337-04 / CA / NCI NIH HHS / United States
R01CA125612 / CA / NCI NIH HHS / United States