A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer. Issue 11 (4th May 2015)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Prostate. Volume 75:Issue 11(2015)
• Page Start: 1206
• Page End: 1215
• Publication Date: 2015-05-04
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.23003
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros23003-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Loss of the phosphatase and tensin homolog (<italic>PTEN</italic>) 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 <italic>PTEN</italic> alterations to predict aggressive disease in a multicenter study.</p> </sec> <sec id="pros23003-sec-0002" sec-type="section"> <title>METHODS</title> <p>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.</p> </sec> <sec id="pros23003-sec-0003" sec-type="section"> <title>RESULTS</title> <p>In 612 prostate cancers, the overall rate of <italic>PTEN</italic> deletion was 112 (18.3%). Hemizygous <italic>PTEN</italic> losses were present in 55/612 (9.0%) of cancers, whereas homozygous <italic>PTEN</italic> deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between <italic>PTEN</italic> status and pathologic stage (<italic>P</italic> < 0.0001), seminal vesicle invasion (<italic>P</italic> = 0.0008), extracapsular extension (<italic>P</italic> < 0.0001), and Gleason score (<italic>P</italic> = 0.0002). In logistic regression analysis of clinical and pathological variables, <italic>PTEN</italic> deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, <italic>PTEN</italic> homozygous (<italic>P</italic> = 0.009) deletion was associated with worse post‐operative recurrence‐free survival (number of events = 189), pre‐operative prostate specific antigen (PSA) (<italic>P</italic> < 0.001), and pathologic stage (<italic>P</italic> = 0.03).</p> </sec> <sec id="pros23003-sec-0004" sec-type="section"> <title>CONCLUSION</title> <p> <italic>PTEN</italic> 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 <italic>HER2/neu</italic> status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a <italic>PTEN</italic> assay in the clinic. <italic>Prostate 75: 1206–1215, 2015</italic>. © 2015 The Authors. <italic>The Prostate</italic>, published by Wiley Periodicals, Inc.</p> </sec> </abstract>