Prevalence of TMPRSS2-ERG Fusion Prostate Cancer among Men Undergoing Prostate Biopsy in the United States

Clinical Cancer Research - Tập 15 Số 14 - Trang 4706-4711 - 2009
Juan Miguel Mosquera1,2, Rohit Mehra3,4, Meredith M. Regan5,2, Sven Perner6,1,2, Elizabeth M. Genega2,7, Gerri Bueti8,9, Rajal B. Shah3,10,11,12,4, Sandra M. Gaston2,13, Scott A. Tomlins3,4, John T. Wei3,10,12,4, Michael Kearney2,8,9, Laura A. Johnson1, Jeffrey M. Tang1, Arul M. Chinnaiyan3,10,11,12,4, Mark A. Rubin14,5,1,2, Martin G. Sanda2,8,9
11Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts,
22Harvard Medical School, Boston, Massachusetts.
33Pathology and
4Pathology, and
512Dana-Farber Harvard Comprehensive Cancer Center, Boston, Massachusetts
610University of Ulm, Department of Pathology, Ulm, Germany,
75Department of Pathology,
86Urology, and
9Urology, and
104Urology, University of Michigan, Ann Arbor, Michigan,
118Michigan Urology Center and
129Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan,
137Surgical Research, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts,
1411Broad Institute of MIT and Harvard Medical School, Cambridge, Massachusetts, and

Tóm tắt

Abstract Purpose: Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in samples of transurethral resection of the prostate from a Swedish cohort of patients with incidental prostate cancer followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific antigen–screened men undergoing prostate biopsy in the United States. Experimental Design: We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization assay. One hundred and thirty-four samples (100 cancer and 34 benign) were assessable. Results: ERG gene rearrangement was detected in 46% of prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (P < 0.0001). Evaluation of morphologic features showed that cribriform growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion–positive prostate cancer biopsies than gene fusion–negative prostate cancer biopsies (P ≤ 0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (P = 0.02). Conclusions: This is the first prospective North American multicenter study to characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphologic features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.

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Tài liệu tham khảo

Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005;310:644–8.

Demichelis F, Fall K, Perner S, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 2007;26:4596–9.

Perner S, Demichelis F, Beroukhim R, et al. TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res 2006;66:8337–41.

Cerveira N, Ribeiro FR, Peixoto A, et al. TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia 2006;8:826–32.

Mehra R, Tomlins SA, Shen R, et al. Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod Pathol 2007;20:538–44.

Rajput AB, Miller MA, De Luca A, et al. Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers. J Clin Pathol 2007;60:1238–43.

Attard G, Clark J, Ambroisine L, et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene 2008;27:253–63.

Nam RK, Sugar L, Yang W, et al. Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br J Cancer 2007;97:1690–5.

Mosquera JM, Perner S, Demichelis F, et al. Morphological features of TMPRSS2-ERG gene fusion prostate cancer. J Pathol 2007;212:91–101.

Perner S, Mosquera JM, Demichelis F, et al. TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol 2007;31:882–8.

Wang J, Cai Y, Ren C, Ittmann M. Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res 2006;66:8347–51.

Svensson M, Perner S, Demichelis F, et al. Frequency of ERG rearrangement in a Swedish hospital based biopsy cohort [abstract 885]. Boston (MA): USCAP; 2009.

Fine S, Gopalan A, Leversha M, et al. Are there morphologic correlates of prostate cancer associated with TMPRSS2-ERG molecular abnormalities? [abstract 659]. San Diego (CA): USCAP; 2007.

Nigwekar P, Miick S, Rittenhouse H, et al. Morphologic correlates of individual splice variants of TMPRSS2-ERG prostate cancer (PCa) detected by transcription-mediated amplification (TMA) in radical prostatectomy (RP) specimens [abstract 797]. Denver (CO): USCAP; 2008.

Barry M, Perner S, Demichelis F, Rubin MA. TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications. Urology 2007;70:630–3.

Mosquera JM, Perner S, Genega EM, et al. Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications. Clin Cancer Res 2008;14:3380–5.

Hessels D, Smit FP, Verhaegh GW, Witjes JA, Cornel EB, Schalken JA. Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin Cancer Res 2007;13:5103–8.

Laxman B, Morris DS, Yu J, et al. A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res 2008;68:645–9.

Laxman B, Tomlins SA, Mehra R, et al. Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia 2006;8:885–8.

Zhou M, Simmerman K, Tsuzuki T, et al. TMPRSS2-ERG gene fusion in prostate cancer of different ethnic groups [abstract 925]. Boston (MA): USCAP; 2009.

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Clinical Cancer Research

Tập 15 Số 14

4706-4711

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