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

• DOI: 10.1038/modpathol.3800981
• Publication Date: 2007-12-07T15:09:53Z
• Authors: Bungo Furusato; Chun-Ling Gao; Lakshmi Ravindranath; Yongmei Chen; Jennifer Cullen; David G McLeod; Albert Dobi; Shiv Srivastava; Gyorgy Petrovics; Isabell A Sesterhenn
• Keywords: Male; Prostatectomy; Prostatic Intraepithelial Neoplasia; Oncogene Proteins, Fusion; Reverse Transcriptase Polymerase Chain Reaction; Prostate; Prostatic Neoplasms; Adenocarcinoma; Middle Aged; Prostate-Specific Antigen; Proto-Oncogene Mas; Disease-Free Survival; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Biomarkers, Tumor; Humans; RNA, Neoplasm; Neoplasm Recurrence, Local; Microdissection; Precancerous Conditions

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.