A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

Dean A. Troyer, Tamara Jamaspishvili, Wei Wei, Ziding Feng, Jennifer Good, Sarah Hawley, Ladan Fazli, Jesse K. McKenney, Jeff Simko, Antonio Hurtado-Coll, Peter R. Carroll, Martin Gleave, Raymond Lance, Daniel W. Lin, Peter S. Nelson, Ian M. Thompson, Lawrence D. True, James D. Brooks, Jeremy A. Squire

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

BACKGROUND. Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. METHODS. We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. RESULTS. In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION. PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic.

Original languageEnglish (US)
Pages (from-to)1206-1215
Number of pages10
JournalProstate
Volume75
Issue number11
DOIs
StatePublished - Aug 1 2015

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Seminal Vesicles
Phosphoric Monoester Hydrolases
Multicenter Studies
Prostatic Neoplasms
Neoplasm Grading
Prostate-Specific Antigen
Biomarkers
Canaries
Tensins
Watchful Waiting
Recurrence
Neoplasms
Prostatectomy
Tumor Suppressor Genes
Disease-Free Survival
Retrospective Studies
Color
Logistic Models
Regression Analysis
Breast Neoplasms

Keywords

  • active surveillance
  • biomarker
  • fluorescence in situ hybridization
  • Gleason score
  • PI3K/PTEN/Akt pathway
  • tissue array analysis

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer. / Troyer, Dean A.; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K.; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R.; Gleave, Martin; Lance, Raymond; Lin, Daniel W.; Nelson, Peter S.; Thompson, Ian M.; True, Lawrence D.; Brooks, James D.; Squire, Jeremy A.

In: Prostate, Vol. 75, No. 11, 01.08.2015, p. 1206-1215.

Research output: Contribution to journalArticle

Troyer, DA, Jamaspishvili, T, Wei, W, Feng, Z, Good, J, Hawley, S, Fazli, L, McKenney, JK, Simko, J, Hurtado-Coll, A, Carroll, PR, Gleave, M, Lance, R, Lin, DW, Nelson, PS, Thompson, IM, True, LD, Brooks, JD & Squire, JA 2015, 'A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer', Prostate, vol. 75, no. 11, pp. 1206-1215. https://doi.org/10.1002/pros.23003
Troyer, Dean A. ; Jamaspishvili, Tamara ; Wei, Wei ; Feng, Ziding ; Good, Jennifer ; Hawley, Sarah ; Fazli, Ladan ; McKenney, Jesse K. ; Simko, Jeff ; Hurtado-Coll, Antonio ; Carroll, Peter R. ; Gleave, Martin ; Lance, Raymond ; Lin, Daniel W. ; Nelson, Peter S. ; Thompson, Ian M. ; True, Lawrence D. ; Brooks, James D. ; Squire, Jeremy A. / A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer. In: Prostate. 2015 ; Vol. 75, No. 11. pp. 1206-1215.
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title = "A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer",
abstract = "BACKGROUND. Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. METHODS. We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. RESULTS. In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3{\%}). Hemizygous PTEN losses were present in 55/612 (9.0{\%}) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3{\%}) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION. PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic.",
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TY - JOUR

T1 - A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

AU - Troyer, Dean A.

AU - Jamaspishvili, Tamara

AU - Wei, Wei

AU - Feng, Ziding

AU - Good, Jennifer

AU - Hawley, Sarah

AU - Fazli, Ladan

AU - McKenney, Jesse K.

AU - Simko, Jeff

AU - Hurtado-Coll, Antonio

AU - Carroll, Peter R.

AU - Gleave, Martin

AU - Lance, Raymond

AU - Lin, Daniel W.

AU - Nelson, Peter S.

AU - Thompson, Ian M.

AU - True, Lawrence D.

AU - Brooks, James D.

AU - Squire, Jeremy A.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - BACKGROUND. Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. METHODS. We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. RESULTS. In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION. PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic.

AB - BACKGROUND. Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. METHODS. We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. RESULTS. In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION. PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic.

KW - active surveillance

KW - biomarker

KW - fluorescence in situ hybridization

KW - Gleason score

KW - PI3K/PTEN/Akt pathway

KW - tissue array analysis

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U2 - 10.1002/pros.23003

DO - 10.1002/pros.23003

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