News  07 Dec.2013

Katri A. Leinonen1,3,4, Outi R. Saramäki1,3,4, Bungo Furusato6, Takahiro Kimura7, Hiroyuki Takahashi6, Shin Egawa7, Hiroyoshi Suzuki8, Kerri Keiger9, Sung Ho Hahm9, and Tapio Visakorpi1,3,4

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 

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.

Cancer Epidemiol Biomarkers Prev December 2013 22; 2333/ ©2013 American Association for Cancer Research.