PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients

Lotan, Tamara L.; Gürel, Bora; Sutcliffe, Siobhan; Esopi, David; Liu, Wennuan; Xu, Jianfeng; Hicks, Jessica L.; Park, Ben Ho; Humphreys, Elizabeth B.; Partin, Alan W.; Han, Misop; Netto, George J.; Isaacs, William B.; Marzo, Angelo M. De

doi:10.1158/1078-0432.ccr-11-1244

Cited by 322 publications

(376 citation statements)

References 41 publications

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“…16 Therefore, there may be patients in our cohort with PTEN loss at the protein level who were not identified using FISH. Our results could potentially be further strengthened with additional IHC.…”

Section: Discussionmentioning

confidence: 99%

Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence

Jeldres

Glaskova

et al. 2016

The Journal of Molecular Diagnostics

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Multiple biomarkers are needed to distinguish aggressive from indolent prostate cancer. We tested the prognostic utility of a three-marker fluorescent in situ hybridization (FISH) panel (TMPRSS2/ERG rearrangements, AR gain, and PTEN deletion) in a retrospective cohort (n Z 210; median follow-up, 5.7 years). PTEN deletion was associated with an increased risk of biochemical recurrence (BcR; hazard ratio, 3.58; 95% CI, 1.39e9.22; P < 0.01) by multivariable Cox regression analyses and earlier BcR (P < 0.02) by Kaplan-Meier analysis. AR gain coexisted with X-chromosome gain and was associated with advanced tumor stage. When this panel was applied, two categories of combinatorial abnormalities proved clinically important. First, PTEN deletion without TMPRSS2/ERG rearrangement was enriched in pT3/4 tumors (70% versus 48%) and tumors with Gleason grades of 8 to 9 (60% versus 17%) compared with the entire cohort. These patients had earlier BcR than patients with normal FISH panel results (P < 0.01). In contrast, patients with PTEN deletion and ERG rearrangement had a BcR rate similar to patients who tested normal for all three markers (P > 0.1). Second, AR gain and concurrent trisomy 10 without TMPRSS2/ERG rearrangement were enriched in pT3/4 tumors and tumors with Gleason grades of 8 to 9. The three-marker FISH panel demonstrated prognostic utility and identified genomic aberrations associated with advanced disease state and early BcR in prostate cancer. (J Mol Diagn 2016, 18: 215e224; http://dx

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Section: Discussionmentioning

confidence: 99%

Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence

Jeldres

Glaskova

et al. 2016

The Journal of Molecular Diagnostics

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“…Phosphatase and tensin homolog (PTEN) is the most commonly inactivated tumor suppressor in prostate cancer (1)(2)(3)(4)(5), and its loss is associated with aggressive clinical-pathologic features (6)(7)(8)(9)(10)(11)(12) and development of castration resistant disease (13)(14)(15)(16). PTEN inactivation may promote castration-resistant tumor growth through upregulation of oncogenic Akt/mTOR signaling (17,18), suppression of androgen receptor (AR) transcription factor activity, and inhibition of AR-regulated negative feedback of Akt (15).…”

Section: Articlementioning

confidence: 99%

“…Addressing this issue, our group previously optimized an immunohistochemistry (IHC) assay for in situ PTEN protein detection in prostate cancer (6). Using this IHC assay, PTEN loss has been associated with biopsy upgrading (20), biochemical recurrence (7,9), and metastatic progression in a high-risk cohort (6).…”

Section: Articlementioning

confidence: 99%

A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer

Ahearn¹,

Pettersson²,

Ebot³

et al. 2015

JNCI.J

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“…Specifically, PTEN loss appears to be associated with increasing likelihood of advanced grade and stage, as well as early recurrence after treatment. 80–82 As such, PTEN loss detected by either fluorescence in situ hybridization or immunohistochemical staining has been proposed for prognostic use. One report from the Transatlantic Prostate Group investigated PTEN in men with conservatively managed prostate cancer with favorable disease characteristics.…”

Section: Molecular Testing In Active Surveillancementioning

confidence: 99%

Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools

Tosoian¹,

Loeb²,

Epstein³

et al. 2016

American Society of Clinical Oncology Educational Book

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Active surveillance (AS) has emerged as a standard management option for men with very low-risk and low-risk prostate cancer, and contemporary data indicate that use of AS is increasing in the United States and abroad. In the favorable-risk population, reports from multiple prospective cohorts indicate a less than 1% likelihood of metastatic disease and prostate cancer-specific mortality over intermediate-term follow-up (median 5 to 6 years). Higher-risk men participating in AS appear to be at increased risk of adverse outcomes, but these populations have not been adequately studied to this point. Although monitoring on AS largely relies on serial prostate biopsy, a procedure associated with significant morbidity, there is a need for improved diagnostic tools for patient selection and monitoring. Revisions from the 2014 International Society of Urologic Pathology consensus conference have yielded a more intuitive reporting system and detailed reporting of low-intermediate grade tumors, which should facilitate the practice of AS. Meanwhile, emerging modalities such as multiparametric magnetic resonance imaging and tissue-based molecular testing have shown prognostic value in some populations. At this time, however, these instruments have not been sufficiently studied to consider their routine, standardized use in the AS setting. Future studies should seek to identify those platforms most informative in the AS population and propose a strategy by which promising diagnostic tools can be safely and efficiently incorporated into clinical practice.

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PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients

Cited by 322 publications

References 41 publications

Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence

Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence

A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer

Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools

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