BACKGROUND: Fusion of the androgen-regulated gene transmembrane protease, serine 2, TMPRSS2, to the v-ets erythroblastosis virus E26 oncogene homolog (avian), ERG, of the erythroblast transformation-specific (ETS) family is the most common genetic alteration in prostate cancer (PCa). OBJECTIVE: To determine whether expression of androgen-regulated TMPRSS2-ERG predicts response to endocrine treatment in hormone-naïve, node-positive PCa. DESIGN, SETTING, AND PARTICIPANTS: Eighty-five patients with histologically confirmed, node-positive PCa who were without treatment at the moment of lymph node dissection were analysed. RNA was isolated from the paraffin-embedded lymph node metastases and complementary DNA (cDNA) was made. The quality of cDNA was tested by polymerase chain reaction (PCR) analysis of the expression of the housekeeping gene hydroxymethylbilane synthase, HMBS (formerly PBGD). TMPRSS2-ERG expression was analysed by PCR using a forward primer in TMPRSS2 exon 1 and a reverse primer in ERG exon 4. MEASUREMENTS: The primary end point was time from start of endocrine therapy to the occurrence of three consecutive rises in prostate-specific antigen (PSA) that were at least 2 wk apart and resulted in two 50% increases over the PSA nadir. Secondary end points were time to PSA nadir after start of endocrine treatment and cancer-specific and overall survival. RESULTS AND LIMITATIONS: TMPRSS2-ERG was expressed in 59% of the 71 patients who could be analysed. Median duration of response to endocrine therapy was 20.9 mo versus 24.1 mo for gene fusion-positive versus gene fusion-negative patients (95% confidence intervals: 18.6-23.1 vs 18.9-29.4, p=0.70). Furthermore, no significant differences were seen between the two groups for the secondary end points. CONCLUSIONS: Expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy. Our results suggest that expression of TMPRSS2-ERG is not a candidate marker to select for metastatic PCa patients who will benefit more from endocrine treatment.
BACKGROUND: Fusion of the androgen-regulated gene transmembrane protease, serine 2, TMPRSS2, to the v-ets erythroblastosis virus E26 oncogene homolog (avian), ERG, of the erythroblast transformation-specific (ETS) family is the most common genetic alteration in prostate cancer (PCa). OBJECTIVE: To determine whether expression of androgen-regulated TMPRSS2-ERG predicts response to endocrine treatment in hormone-naïve, node-positive PCa. DESIGN, SETTING, AND PARTICIPANTS: Eighty-five patients with histologically confirmed, node-positive PCa who were without treatment at the moment of lymph node dissection were analysed. RNA was isolated from the paraffin-embedded lymph node metastases and complementary DNA (cDNA) was made. The quality of cDNA was tested by polymerase chain reaction (PCR) analysis of the expression of the housekeeping gene hydroxymethylbilane synthase, HMBS (formerly PBGD). TMPRSS2-ERG expression was analysed by PCR using a forward primer in TMPRSS2 exon 1 and a reverse primer in ERG exon 4. MEASUREMENTS: The primary end point was time from start of endocrine therapy to the occurrence of three consecutive rises in prostate-specific antigen (PSA) that were at least 2 wk apart and resulted in two 50% increases over the PSA nadir. Secondary end points were time to PSA nadir after start of endocrine treatment and cancer-specific and overall survival. RESULTS AND LIMITATIONS: TMPRSS2-ERG was expressed in 59% of the 71 patients who could be analysed. Median duration of response to endocrine therapy was 20.9 mo versus 24.1 mo for gene fusion-positive versus gene fusion-negative patients (95% confidence intervals: 18.6-23.1 vs 18.9-29.4, p=0.70). Furthermore, no significant differences were seen between the two groups for the secondary end points. CONCLUSIONS: Expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy. Our results suggest that expression of TMPRSS2-ERG is not a candidate marker to select for metastatic PCa patients who will benefit more from endocrine treatment.
Authors: Rebecca E Graff; Andreas Pettersson; Rosina T Lis; Natalie DuPre; Kristina M Jordahl; Elizabeth Nuttall; Jennifer R Rider; Michelangelo Fiorentino; Howard D Sesso; Stacey A Kenfield; Massimo Loda; Edward L Giovannucci; Bernard Rosner; Paul L Nguyen; Christopher J Sweeney; Lorelei A Mucci Journal: Prostate Date: 2015-03-01 Impact factor: 4.104
Authors: Gina M Sizemore; Jason R Pitarresi; Subhasree Balakrishnan; Michael C Ostrowski Journal: Nat Rev Cancer Date: 2017-04-28 Impact factor: 60.716
Authors: Andreas Pettersson; Rebecca E Graff; Scott R Bauer; Michael J Pitt; Rosina T Lis; Edward C Stack; Neil E Martin; Lauren Kunz; Kathryn L Penney; Azra H Ligon; Catherine Suppan; Richard Flavin; Howard D Sesso; Jennifer R Rider; Christopher Sweeney; Meir J Stampfer; Michelangelo Fiorentino; Philip W Kantoff; Martin G Sanda; Edward L Giovannucci; Eric L Ding; Massimo Loda; Lorelei A Mucci Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-06-26 Impact factor: 4.254
Authors: David S Rickman; Ying-Bei Chen; Samprit Banerjee; Yihang Pan; Jindan Yu; Terry Vuong; Sven Perner; Christopher J Lafargue; Kirsten D Mertz; Sunita R Setlur; Kanishka Sircar; Arul M Chinnaiyan; Tarek A Bismar; Mark A Rubin; Francesca Demichelis Journal: Neoplasia Date: 2010-12 Impact factor: 5.715
Authors: Katri A Leinonen; Outi R Saramäki; Bungo Furusato; Takahiro Kimura; Hiroyuki Takahashi; Shin Egawa; Hiroyoshi Suzuki; Kerri Keiger; Sung Ho Hahm; William B Isaacs; Teemu T Tolonen; Ulf-Håkan Stenman; Teuvo L J Tammela; Matti Nykter; G Steven Bova; Tapio Visakorpi Journal: Cancer Epidemiol Biomarkers Prev Date: 2013-10-01 Impact factor: 4.254
Authors: Timothy N Clinton; Aditya Bagrodia; Yair Lotan; Vitaly Margulis; Ganesh V Raj; Solomon L Woldu Journal: Expert Rev Precis Med Drug Dev Date: 2017-09-05