Will Biomarkers Save Prostate Cancer Screening?

Cooperberg, Matthew R.

doi:10.1016/j.eururo.2012.06.034

Cited by 5 publications

(2 citation statements)

References 10 publications

(8 reference statements)

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“…Radical prostatectomy and radiation therapy are treatments that offer high cure rates; however, it is estimated that over 1,055 men need to be screened and 37 cancers detected to prevent one prostate cancer death 11 years later . Recently, recommendations for screening have been narrowed , and active surveillance protocols are commonly recommended for men with low risk disease . Prognostic biomarkers are needed to aid in clinical decision making for these men to more accurately distinguish between low risk and moderate to high risk prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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BACKGROUNDLoss 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.METHODSWe 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.RESULTSIn 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).CONCLUSIONPTEN 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. Prostate 75: 1206–1215, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…Definitive treatment with radical prostatectomy or radiation therapy are essentially curative, however, it is estimated that over 1,055 men need to be screened and 37 cancers detected to prevent one prostate cancer death 11 years later (Schröder et al, ). There is a need for improved biomarkers for detection of aggressive disease (Cooperberg, ), and selection of men who may benefit from active surveillance protocols (Dall'Era et al, ; Bangma et al, ). Nevertheless, prostate cancer (PCa) is the second leading cause of death among men in the United States (Cazares et al, ; Saron et al, ; Barlow and Shen, ).…”

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confidence: 99%

Complex‐I Alteration and Enhanced Mitochondrial Fusion Are Associated With Prostate Cancer Progression

Philley

Kannan

Qin

et al. 2015

Journal Cellular Physiology

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Mitochondria (mt) encoded respiratory complex-I (RCI) mutations and their pathogenicity remain largely unknown in prostate cancer (PCa). Little is known about the role of mtDNA loss on mt integrity in PCa. We determined mtDNA mutation in human and mice PCa and assessed the impact of mtDNA depletion on mt integrity. We also examined whether the circulating exosomes from PCa patients are transported to mt and carry mtDNA or mt proteins. We have employed next generation sequencing of the whole mt genome in human and Hi-myc PCa. The impact of mtDNA depletion on mt integrity, presence of mtDNA, and protein in sera exosomes was determined. A co-culture of human PCa cells and the circulating exosomes followed by confocal imaging determined co-localization of exosomes and mt. We observed frequent RCI mutations in human and Hi-myc PCa which disrupted corresponding complex protein expression. Depletion of mtDNA in PCa cells influenced mt integrity, increased expression of MFN1, MFN2, PINK1, and decreased expression of MT-TFA. Increased mt fusion and expression of PINK1 and DNM1L were also evident in the Hi-myc tumors. RCI-mtDNA, MFN2, and IMMT proteins were detected in the circulating exosomes of men with benign prostate hyperplasia (BPH) and progressive PCa. Circulating exosomes and mt co-localized in PCa cells. Our study identified new pathogenic RCI mutations in PCa and defined the impact of mtDNA loss on mt integrity. Presence of mtDNA and mt proteins in the circulating exosomes implicated their usefulness for biomarker development.

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Reply from Authors re: Matthew R. Cooperberg. Will Biomarkers Save Prostate Cancer Screening? Eur Urol 2012;62:962–3

Kader

2012

European Urology

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Will Biomarkers Save Prostate Cancer Screening?

Cited by 5 publications

References 10 publications

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

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

Complex‐I Alteration and Enhanced Mitochondrial Fusion Are Associated With Prostate Cancer Progression

Reply from Authors re: Matthew R. Cooperberg. Will Biomarkers Save Prostate Cancer Screening? Eur Urol 2012;62:962–3

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