Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer

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

Research output: Contribution to journalArticle

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.Whenmetastases 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.

Original languageEnglish (US)
Pages (from-to)2333-2344
Number of pages12
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number12
DOIs
StatePublished - Dec 2013

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Prostatic Neoplasms
Castration
Prostatectomy
Neoplasm Metastasis
Sequence Deletion
Needle Biopsy
Disease-Free Survival
Disease Progression
Multivariate Analysis
Immunohistochemistry
Mutation
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Leinonen, K. A., Saramäki, O. R., Furusato, B., Kimura, T., Takahashi, H., Egawa, S., ... Visakorpi, T. (2013). Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer. Cancer Epidemiology Biomarkers and Prevention, 22(12), 2333-2344. https://doi.org/10.1158/1055-9965.EPI-13-0333-T

Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer. / Leinonen, Katri A.; Saramäki, Outi R.; Furusato, Bungo; Kimura, Takahiro; Takahashi, Hiroyuki; Egawa, Shin; Suzuki, Hiroyoshi; Keiger, Kerri; Hahm, Sung Ho; Isaacs, William B; Tolonen, Teemu T.; Stenman, Ulf Håkan; Tammela, Teuvo L J; Nykter, Matti; Bova, G. Steven; Visakorpi, Tapio.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 12, 12.2013, p. 2333-2344.

Research output: Contribution to journalArticle

Leinonen, KA, Saramäki, OR, Furusato, B, Kimura, T, Takahashi, H, Egawa, S, Suzuki, H, Keiger, K, Hahm, SH, Isaacs, WB, Tolonen, TT, Stenman, UH, Tammela, TLJ, Nykter, M, Bova, GS & Visakorpi, T 2013, 'Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 12, pp. 2333-2344. https://doi.org/10.1158/1055-9965.EPI-13-0333-T
Leinonen, Katri A. ; Saramäki, Outi R. ; Furusato, Bungo ; Kimura, Takahiro ; Takahashi, Hiroyuki ; Egawa, Shin ; Suzuki, Hiroyoshi ; Keiger, Kerri ; Hahm, Sung Ho ; Isaacs, William B ; Tolonen, Teemu T. ; Stenman, Ulf Håkan ; Tammela, Teuvo L J ; Nykter, Matti ; Bova, G. Steven ; Visakorpi, Tapio. / Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 12. pp. 2333-2344.
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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.Whenmetastases 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.",
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T1 - Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer

AU - Leinonen, Katri A.

AU - Saramäki, Outi R.

AU - Furusato, Bungo

AU - Kimura, Takahiro

AU - Takahashi, Hiroyuki

AU - Egawa, Shin

AU - Suzuki, Hiroyoshi

AU - Keiger, Kerri

AU - Hahm, Sung Ho

AU - Isaacs, William B

AU - Tolonen, Teemu T.

AU - Stenman, Ulf Håkan

AU - Tammela, Teuvo L J

AU - Nykter, Matti

AU - Bova, G. Steven

AU - Visakorpi, Tapio

PY - 2013/12

Y1 - 2013/12

N2 - 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.Whenmetastases 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.

AB - 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.Whenmetastases 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.

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