Mapping of TMPRSS2-ERG fusions in the context of multi-focal prostate cancer

Mod Pathol. 2008 Feb;21(2):67-75. doi: 10.1038/modpathol.3800981. Epub 2007 Dec 7.

Abstract

TMPRSS2-ERG gene fusion leading to the androgenic induction of the ERG proto-oncogene expression is a highly prevalent oncogenic alteration in prostate tumor cells. Prostate cancer is a multi-focal disease, and the origins as well as biological contribution of multiple cancer foci remain unclear with respect to prostate cancer onset or progression. To assess the role of TMPRSS2-ERG alteration in prostate cancer onset and/or progression, we have evaluated the status of fusion transcripts in benign glands, prostatic intraepithelial neoplasia (PIN) and multiple cancer foci of each prostate. Quantitative expression of TMPRSS2-ERG fusion type A and C transcripts was analyzed in benign, tumor and PIN areas, selected from whole-mount radical prostatectomy slides. TMPRSS2-ERG expression was correlated with clinicopathological features. Overall, 30 of 45 (67%) patients exhibited TMPRSS2-ERG fusion transcripts in at least one tumor focus. Of 80 tumor foci analyzed, 39 had TMPRSS2-ERG fusion (type A only: 30, type C only: 2, both types A and C: 7), with predominant detection of the TMPRSS2-ERG fusion type A (27/30, 90%) in the index tumors. Of 14 PIN lesions, 2 were positive for type A fusion. Frequent presence of the TMPRSS2-ERG in index tumors suggests critical roles of ERG alterations in the onset and progression of a large subset of prostate cancer. However, heterogeneity of the TMPRSS2-ERG detection in the context of multiple cancer foci and its frequency in PIN also support the role of other genomic alterations in the origins of prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Disease-Free Survival
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Microdissection
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Prostate / metabolism
  • Prostate / pathology
  • Prostate / surgery
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Intraepithelial Neoplasia / genetics*
  • Prostatic Intraepithelial Neoplasia / metabolism
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA, Neoplasm / analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • Oncogene Proteins, Fusion
  • RNA, Neoplasm
  • TMPRSS2-ERG fusion protein, human
  • Prostate-Specific Antigen