Loss of PTEN Is Associated with Aggressive Behavior in ERG-Positive Prostate Cancer

Cancer Epidemiology Biomarkers and Prevention - Tập 22 Số 12 - Trang 2333-2344 - 2013
Katri A. Leinonen1, Outi R. Saramäki1, Bungo Furusato1,2, Takahiro Kimura1,2, Hiroyuki Takahashi1,2, Shin Egawa1,2, Hiroyoshi Suzuki1, Kerri Keiger1, Sung‐Ho Hahm1, William B. Isaacs1, Teemu Tolonen1, Ulf‐Håkan Stenman1, Teuvo L.J. Tammela1, Matti Nykter1, G. Steven Bova1, Tapio Visakorpi1
1Authors' Affiliations: 1Institute of Biomedical Technology and 2Institute of Signal Processing, 3Prostate Cancer Research Center, 4BioMediTech, 5Department of Urology, School of Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland; Departments of 6Pathology and 7Urology, Jikei University School of Medicine, Minato-ku, Tokyo; 8Department of Urology, Toho University Sakura Medical Center, Sakura, Chiba, Japan; Departments of 9Pathology and 10Urology, Johns Hopkins University, Baltimore, Maryland; and 11Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland
2the Jikei University School of Medicine

Tóm tắt

Abstract Background: The associations of ERG overexpression with clinical behavior and molecular pathways of prostate cancer are incompletely known. We assessed the association of ERG expression with AR, PTEN, SPINK1, Ki-67, and EZH2 expression levels, deletion, and mutations of chromosomal region 3p14 and TP53, and clinicopathologic variables. Methods: The material consisted of 326 prostatectomies, 166 needle biopsies from men treated primarily with endocrine therapy, 177 transurethral resections of castration-resistant prostate cancers (CRPC), and 114 CRPC metastases obtained from 32 men. Immunohistochemistry, FISH, and sequencing was used for the measurements. Results: ERG expression was found in about 45% of all patient cohorts. In a multivariate analysis, ERG expression showed independent value of favorable prognosis (P = 0.019). ERG positivity was significantly associated with loss of PTEN expression in prostatectomy (P = 0.0348), and locally recurrent CRPCs (P = 0.0042). Loss of PTEN expression was associated (P = 0.0085) with shorter progression-free survival in ERG-positive, but not in negative cases. When metastases in each subject were compared, consistent ERG, PTEN, and AR expression as well as TP53 mutations were found in a majority of subjects. Conclusions: A similar frequency of ERG positivity from early to late stage of the disease suggests lack of selection of ERG expression during disease progression. The prognostic significance of PTEN loss solely in ERG-positive cases indicates interaction of these pathways. The finding of consistent genetic alterations in different metastases suggests that the major genetic alterations take place in the primary tumor. Impact: Interaction of PTEN and ERG pathways warrants further studies. Cancer Epidemiol Biomarkers Prev; 22(12); 2333–44. ©2013 AACR.

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Cancer Epidemiology Biomarkers and Prevention

Tập 22 Số 12

2333-2344

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