Article

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

Department of Surgery, United States Military Cancer Institute, Center for Prostate Disease Research, Uniformed Service University of the Health Science, Bethesda, MD, USA.
Modern Pathology (impact factor: 4.79). 03/2008; 21(2):67-75. DOI:10.1038/modpathol.3800981 pp.67-75
Source: PubMed

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.

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Keywords

benign glands
 
biological contribution
 
clinicopathological features
 
ERG proto-oncogene expression
 
index tumors
 
large subset
 
multi-focal disease
 
one tumor focus
 
PIN areas
 
predominant detection
 
prevalent oncogenic alteration
 
prostate cancer
 
prostate cancer onset
 
prostate tumor cells
 
prostatic intraepithelial neoplasia
 
TMPRSS2-ERG alteration
 
TMPRSS2-ERG detection
 
TMPRSS2-ERG gene fusion
 
type C
 
whole-mount radical prostatectomy