The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: A cohort study and meta-analysis

Cancer Epidemiology Biomarkers and Prevention

Volumn 21, Issue 9, 2012, Pages 1497-1509

  Pettersson, Andreas ^a,b   Graff, Rebecca E ^a,b   Bauer, Scott R ^b,f   Pitt, Michael J ^a,b   Lis, Rosina T ^a,c   Stack, Edward C ^a,c   Martin, Neil E ^c   Kunz, Lauren ^b   Penney, Kathryn L ^a,b   Ligon, Azra H ^a,c   Suppan, Catherine ^a   Flavin, Richard ^c,g   Sesso, Howard D ^a   Rider, Jennifer R ^a,b   Sweeney, Christopher ^d   Stampfer, Meir J ^a,b   Fiorentino, Michelangelo ^b,c,h   Kantoff, Philip W ^d   Sanda, Martin G ^e   Giovannucci, Edward L ^a,b   Ding, Eric L ^a,b   Loda, Massimo ^a,c   Mucci, Lorelei A ^a,b   more..

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^c DANA FARBER CANCER INSTITUTE   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g NATIONAL UNIVERSITY OF IRELAND   (Ireland)

^h UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEINASE; TRANSCRIPTION FACTOR ERG; TRANSMEMBRANE PROTEASE SERINE 2; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CANCER MORTALITY; CANCER PROGNOSIS; CANCER RECURRENCE; CANCER STAGING; CANCER SURGERY; COHORT ANALYSIS; DISTANT METASTASIS; FOLLOW UP; GENE EXPRESSION; GENE OVEREXPRESSION; GENE REARRANGEMENT; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MAJOR CLINICAL STUDY; MALE; META ANALYSIS; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROSPECTIVE STUDY; PROSTATE CANCER; PROSTATECTOMY; PROTEIN EXPRESSION;

AGED; COHORT STUDIES; GENE FUSION; GENE REARRANGEMENT; HUMANS; MALE; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; NEOPLASM STAGING; PROSTATIC NEOPLASMS; SERINE ENDOPEPTIDASES; TRANS-ACTIVATORS; TREATMENT OUTCOME;

EID: 84866172302     PISSN: 10559965     EISSN: None     Source Type: Journal    
DOI: 10.1158/1055-9965.EPI-12-0042     Document Type: Article

References (83)

1. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005;310:644-8.
2. Frohling S, Dohner H. Chromosomal abnormalities in cancer. N Engl J Med 2008;359:722-34.
3. Tomlins SA, Bjartell A, Chinnaiyan AM, Jenster G, Nam RK, Rubin MA, et al. ETS gene fusions in prostate cancer: from discovery to daily clinical practice. Eur Urol 2009;56:275-86.
4. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011;61:212-36.
5. Hermans KG, van Marion R, van Dekken H, Jenster G, van Weerden WM, Trapman J. TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer. Cancer Res 2006;66:10658-63.
6. Perner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera JM, Setlur S, et al. TMPRSS2: ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res 2006;66:8337-41.
7. Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, et al. Prostate-localized and androgen-regulated expression of the membrane- bound serine protease TMPRSS2. Cancer Res 1999;59:4180-4.
8. Seth A, Watson DK. ETS transcription factors and their emerging roles in human cancer. Eur J Cancer 2005;41:2462-78.
9. Clark JP, Cooper CS. ETS gene fusions in prostate cancer. Nat Rev Urol 2009;6:429-39.
10. Attard G, Clark J, Ambroisine L, Fisher G, Kovacs G, Flohr P, et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene 2008;27:253-63.
11. Demichelis F, Fall K, Perner S, Andren O, Schmidt F, Setlur SR, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 2007;26:4596-9.
12. Nam RK, Sugar L, Yang W, Srivastava S, Klotz LH, Yang LY, 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.
13. 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.
14. Yoshimoto M, Joshua AM, Cunha IW, Coudry RA, Fonseca FP, Ludkovski O, et al. Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome. Mod Pathol 2008;21:1451-60.
15. Gopalan A, Leversha MA, Satagopan JM, Zhou Q, Al-Ahmadie HA, Fine SW, et al. TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res 2009;69:1400-6.
16. Lapointe J, Kim YH, Miller MA, Li C, Kaygusuz G, Van De Rijn M, et al. A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis. Mod Pathol 2007;20:467-73.
17. Rostad K, Hellwinkel OJ, Haukaas SA, Halvorsen OJ, Oyan AM, Haese A, et al. TMPRSS2:ERGfusion transcripts in urine from prostate cancer patients correlate with a less favorable prognosis. APMIS 2009;117:575-82.
18. Hofer MD, Kuefer R, Maier C, Herkommer K, Perner S, Demichelis F, et al. Genome-wide linkage analysis of TMPRSS2-ERG fusion in familial prostate cancer. Cancer Res 2009;69:640-6.
19. Lee K, Chae JY, Kwak C, Ku JH, Moon KC. TMPRSS2-ERG gene fusion and clinicopathologic characteristics of Korean prostate cancer patients. Urology 2010;76:1268.e7-13.
20. Leinonen KA, Tolonen TT, Bracken H, Stenman UH, Tammela TLJ, Saramaki OR, et al. Association of SPINK1 expression and TMPRSS2: ERG fusion with prognosis in endocrine-treated prostate cancer. Clin Cancer Res 2010;16:2845-51.
21. Rouzier C, Haudebourg J, Carpentier X, Valerio L, Amiel J, Michiels JF, et al. Detection of the TMPRSS2-ETS fusion gene in prostate carcinomas: retrospective analysis of 55 formalin-fixed and paraffinembedded samples with clinical data. Cancer Genet Cytogenet 2008;183:21-7.
22. Rubio-Briones J, Fernandez-Serra A, Calatrava A, Garcia-Casado Z, Rubio L, Bonillo MA, et al. Clinical implications of TMPRSS2-ERG gene fusion expression in patients with prostate cancer treated with radical prostatectomy. J Urol 2010;183:2054-61.
23. Saramaki OR, Harjula AE, Martikainen PM, Lvessella R, Tammela TLJ, Visakorpi T. TMPRSS2.ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin Cancer Res 2008;14:3395-400.
24. Toubaji A, Albadine R, Meeker AK, Isaacs WB, Lotan T, Haffner MC, et al. Increased gene copy number of ERG on chromosome 21 but not TMPRSS2-ERG fusion predicts outcome in prostatic adenocarcinomas. Mod Pathol 2011;24:1511-20.
25. Darnel AD, Lafargue CJ, Vollmer RT, Corcos J, Bismar TA. TMPRSS2-ERGfusion is frequently observed in Gleason pattern 3 prostate cancer in a Canadian cohort. Cancer Biol Ther 2009;8:125-30.
26. Minner S, Enodien M, Sirma H, Luebke AM, Krohn A, Mayer PS, et al. ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of anti-hormonal therapy. Clin Cancer Res 2011;17:5878-88.
27. Hermans KG, Boormans JL, Gasi D, Van Leenders GJ, Jenster G, Verhagen PC, et al. Overexpression of prostate-specific TMPRSS2 (exon 0)-ERG fusion transcripts corresponds with favorable prognosis of prostate cancer. Clin Cancer Res 2009;15:6398-403.
28. Mao C, Yu Y, Boyd LK, Ren G, Lin D, Chaplin T, et al. Distinct genomic alterations in prostate cancers in Chinese and western populations suggest alternative pathways of prostate carcinogenesis. Cancer Res 2010;70:5207-12.
29. Miyagi Y, Sasaki T, Fujinami K, Sano J, Senga Y, Miura T, et al. ETS family-associated gene fusions in Japanese prostate cancer: analysis of 194 radical prostatectomy samples. Mod Pathol 2010;23:1492-8.
30. Mosquera JM, Mehra R, Regan MM, Perner S, Genega EM, Bueti G, et al. Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States. Clin Cancer Res 2009;15:4706-11.
31. Sun QP, Li LY, Chen Z, Pang J, Yang WJ, Zhou XF, et al. Detection of TMPRSS2-ETS fusions by a multiprobe fluorescence in situ hybridization assay for the early diagnosis of prostate cancer: a pilot study. J Mol Diagn 2010;12:718-24.
32. Tu JJ, Rohan S, Kao J, Kitabayashi N, Mathew S, Chen Y-T. Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues. Mod Pathol 2007;20:921-8.
33. Magi-Galluzzi C, Tsusuki T, Elson P, Simmerman K, Lafargue C, Esgueva R, et al. TMPRSS2-ERG gene fusion prevalence and class are significantly different in prostate cancer of Caucasian, African-American and Japanese patients. Prostate 2011;71:489-97.
34. Hennekens CH, Eberlein K. A randomized trial of aspirin and betacarotene among U.S. physicians. Prev Med 1985;14:165-8.
35. Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 2009;301:52-62.
36. Stark JR, Perner S, Stampfer MJ, Sinnott JA, Finn S, Eisenstein AS, et al. Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3? J Clin Oncol 2009;27:3459-64.
37. Park K, Tomlins SA, Mudaliar KM, Chiu YL, Esgueva R, Mehra R, et al. Antibody-based detection of ERG rearrangement-positive prostate cancer. Neoplasia 2010;12:590-8.
38. Chaux A, Albadine R, Toubaji A, Hicks J, Meeker A, Platz EA, et al. Immunohistochemistry for ERG expression as a surrogate for TMPRSS2-ERG fusion detection in prostatic adenocarcinomas. Am J Surg Pathol 2011;35:1014-20.
39. van Leenders GJ, Boormans JL, Vissers CJ, Hoogland AM, Bressers AA, Furusato B, et al. Antibody EPR3864 is specific for ERG genomic fusions in prostate cancer: implications for pathological practice. Mod Pathol 2011;24:1128-38.
40. Clark JP, Munson KW, Gu JW, Lamparska-Kupsik K, Chan KG, Yoshida JS, et al. Performance of a single assay for both type III and type VI TMPRSS2:ERG fusions in noninvasive prediction of prostate biopsy outcome. Clin Chem 2008;54:2007-17.
41. Tomlins SA, Aubin SM, Siddiqui J, Lonigro RJ, Sefton-Miller L, Miick S, et al. Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med 2011;3:94ra72.
42. Zhang S, Pavlovitz B, Tull J, Wang Y, Deng FM, Fuller C. Detection of TMPRSS2 gene deletions and translocations in carcinoma, intraepithelial neoplasia, and normal epithelium of the prostate by direct fluorescence in situ hybridization. Diagn Mol Pathol 2010;19:151-6.
43. Rajput AB, Miller MA, De Luca A, Boyd N, Leung S, Hurtado-Coll 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.
44. Bismar TA, Dolph M, Teng LH, Liu S, Donnelly B. ERG protein expression reflects hormonal treatment response and is associated with Gleason score and prostate cancer specific mortality. Eur J Cancer 2012;48:538-46.
45. Guo CC, Dancer JY, Wang Y, Aparicio A, Navone NM, Troncoso P, et al. TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate. Hum Pathol 2011;42:11-7.
46. Lotan TL, Toubaji A, Albadine R, Latour M, Herawi M, Meeker AK, et al. TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas. Mod Pathol 2009;22:359-65.
47. Stott SL, Lee RJ, Nagrath S, Yu M, Miyamoto DT, Ulkus L, et al. Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci Transl Med 2010;2:25ra3.
48. Han B, Suleman K, Wang L, Siddiqui J, Sercia L, Magi-Galluzzi C, et al. ETS gene aberrations in atypical cribriform lesions of the prostate: implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia. Am J Surg Pathol 2010;34:478-85.
49. Danila DC, Anand A, Sung CC, Heller G, Leversha MA, Cao L, et al. TMPRSS2-ERG status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate. Eur Urol 2011;60:897-904.
50. Dhani NC, Emmenegger U, Adams L, Jongstra J, Tannock IF, Sridhar SS, et al. Phase II study of cytarabine in men with docetaxel-refractory, castration-resistant prostate cancer with evaluation of TMPRSS2-ERG and SPINK1 as serum biomarkers. BJU Int. 2012 Feb 7. [Epub ahead of print].
51. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.
52. Paulo P, Barros-Silva JD, Ribeiro FR, Ramalho-Carvalho J, Jeronimo C, Henrique R, et al. FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer. Genes Chromosomes Cancer 2012;51:240-9.
53. Albadine R, Latour M, Toubaji A, Haffner M, Isaacs WB, Platz EA, et al. TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma. Mod Pathol 2009;22:1415-22.
54. Bonaccorsi L, Nesi G, Nuti F, Paglierani M, Krausz C, Masieri L, et al. Persistence of expression of the TMPRSS2:ERG fusion gene after presurgery androgen ablation may be associated with early prostate specific antigen relapse of prostate cancer: preliminary results. J Endocrinol Invest 2009;32:590-6.
55. Falzarano SM, Navas M, Simmerman K, Klein EA, Rubin MA, Zhou M, et al. ERG rearrangement is present in a subset of transition zone prostatic tumors. Mod Pathol 2010;23:1499-506.
56. Falzarano SM, Zhou M, Hernandez AV, Klein EA, Rubin MA, Magi-Galluzzi C. Single focus prostate cancer: pathological features and ERG fusion status. J Urol 2011;185:489-94.
57. FitzGerald LM, Agalliu I, Johnson K, Miller MA, Kwon EM, Hurtado-Coll A, et al. Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer. BMC Cancer 2008;8:230.
58. Furusato B, Gao CL, Ravindranath L, Chen Y, Cullen J, McLeod DG, et al. Mapping of TMPRSS2-ERG fusions in the context of multi-focal prostate cancer. Mod Pathol 2008;21:67-75.
59. Guo CC, Zuo G, Cao D, Troncoso P, Czerniak BA. Prostate cancer of transition zone origin lacks TMPRSS2-ERG gene fusion. Mod Pathol 2009;22:866-71.
60. Laxman B, Tomlins SA, Mehra R, Morris DS, Wang L, Helgeson BE, et al. Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia 2006;8:885-8.
61. Mehra R, Han B, Tomlins SA, Wang L, Menon A, Wasco MJ, et al. Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Cancer Res 2007;67:7991-5.
62. Mehra R, Tomlins SA, Shen R, Nadeem O, Wang L, Wei JT, et al. Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod Pathol 2007;20:538-44.
63. Barros-Silva JD, Ribeiro FR, Rodrigues A, Cruz R, Martins AT, Jeronimo C, et al. Relative 8q gain predicts disease-specific survival irrespective of the TMPRSS2-ERG fusion status in diagnostic biopsies of prostate cancer. Genes Chromosomes Cancer 2011;50:662-71.
64. Boormans JL, Hermans K G, Made AC, van Leenders GJ, Wildhagen MF, Collette L, et al. Expression of the androgen-regulated fusion gene TMPRSS2-ERG does not predict response to endocrine treatment in hormone-naive, node-positive prostate cancer. Eur Urol 2010;57:830-5.
65. Furusato B, Tan SH, Young D, Dobi A, Sun C, Mohamed AA, et al. ERG oncoprotein expression in prostate cancer: clonal progression of ERG positive tumor cells and potential for ERG-based stratification. Prostate Cancer Prostatic Dis 2010;13:228-37.
66. Furusato B, van Leenders GJ, Trapman J, Kimura T, Egawa S, Takahashi H, et al. Immunohistochemical ETS-related gene detection in a Japanese prostate cancer cohort: diagnostic use in Japanese prostate cancer patients. Pathol Int 2011;61:409-14.
67. Mani RS, Iyer MK, Cao Q, Brenner JC, Wang L, Ghosh A, et al. TMPRSS2-ERG-mediated feed-forward regulation of wild-type ERG in human prostate cancers. Cancer Res 2011;71:5387-92.
68. Svensson MA, LaFargue CJ, MacDonald TY, Pflueger D, Kitabayashi N, Santa-Cruz AM, et al. Testing mutual exclusivity of ETS rearranged prostate cancer. Lab Invest 2011;91:404-12.
69. Vainio P, Gupta S, Ketola K, Mirtti T, Mpindi JP, Kohonen P, et al. Arachidonic acid pathway members PLA2G7, HPGD, EPHX2, and CYP4F8 identified as putative novel therapeutic targets in prostate cancer. Am J Pathol 2011;178:525-36.
70. Winnes M, Lissbrant E, Damber JE, Stenman G. Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer. Oncol Rep 2007;17:1033-6.
71. Braun M, Scheble VJ, Menon R, Scharf G, Wilbertz T, Petersen K, et al. Relevance of cohort design for studying the frequency of the ERG rearrangement in prostate cancer. Histopathology 2011;58:1028-36.
72. Hoogland AM, Jenster G, van Weerden WM, Trapman J, van der Kwast T, Roobol MJ, et al. ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer. Mod Pathol 2012;25:471-9.
73. Esgueva R, Perner S, LaFargue C, Scheble V, Stephan C, Lein M, et al. Prevalence of TMPRSS2-ERG and SLC45A3-ERG gene fusions in a large prostatectomy cohort. Mod Pathol 2010;23:539-46.
74. Greene DR, Fitzpatrick JM, Scardino PT. Anatomy of the prostate and distribution of early prostate cancer. Semin Surg Oncol 1995;11:9-22.
75. Bismar TA, Trpkov K. TMPRSS2-ERG gene fusion in transition zone prostate cancer. Mod Pathol 2010;23:1040-1; author reply 1041-2.
76. Liu S, Yoshimoto M, Trpkov K, Duan Q, Firszt M, Corcos J, et al. Detection of ERG gene rearrangements and PTEN deletions in unsuspected prostate cancer of the transition zone. Cancer Biol Ther 2011;11:562-6.
77. Sboner A, Demichelis F, Calza S, Pawitan Y, Setlur SR, Hoshida Y, et al. Molecular sampling of prostate cancer: a dilemma for predicting disease progression. BMC Med Genomics 2010;3:8.
78. King CR, Ferrari M, Brooks JD. Prognostic significance of prostate cancer originating from the transition zone. Urol Oncol 2009;27:592-7.
79. Shah RB, Chinnaiyan AM. The discovery of common recurrent transmembrane protease serine 2 (TMPRSS2)-erythroblastosis virus E26 transforming sequence (ETS) gene fusions in prostate cancer: significance and clinical implications. Adv Anat Pathol 2009;16:145-53.
80. Brenner JC, Ateeq B, Li Y, Yocum AK, Cao Q, Asangani IA, et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell 2011;19:664-78.
81. Swanson TA, Krueger SA, Galoforo S, Thibodeau BJ, Martinez AA, Wilson GD, et al. TMPRSS2/ERG fusion gene expression alters chemo- and radio-responsiveness in cell culture models of androgen independent prostate cancer. Prostate. 2011 Mar 10. [Epub ahead of print].
82. Antonarakis ES, Chen Y, Elsamanoudi SI, Brassell SA, Da Rocha MV, Eisenberger MA, et al. Long-term overall survival and metastasis-free survival for men with prostate-specific antigen-recurrent prostate cancer after prostatectomy: analysis of the Center for Prostate Disease Research National Database. BJU Int 2010;108:378-85.
83. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 2005;294:433-9.