Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN)
Abstract Background Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstra...
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| creator | Jamaspishvili, Tamara Patel, Palak G Niu, Yi Vidotto, Thiago Caven, Isabelle Livergant, Rachel Fu, Winnie Kawashima, Atsunari How, Nathan Okello, John B Guedes, Liana B Ouellet, Veronique Picanço, Clarissa Koti, Madhuri Reis, Rodolfo B Saad, Fred Mes-Masson, Anne-Marie Lotan, Tamara L Squire, Jeremy A Peng, Yingwei P Siemens, D Robert Berman, David M |
| description | Abstract
Background
Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application.
Methods
PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided.
Results
PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.59 to 3.87; P |
| doi_str_mv | 10.1093/jnci/djaa032 |
| format | Article |
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Background
Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application.
Methods
PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided.
Results
PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.59 to 3.87; P < .001) and validation cohorts (HR = 4.22, 95% CI = 2.01 to 8.83; P < .001). The qPTEN scoring method identified patients who recurred within 5.4 years after surgery (P < .001). In men with favorable risk of biochemical recurrence (Cancer of the Prostate Risk Assessment – Postsurgical scores <5 and no adverse pathological features), qPTEN identified a subset of patients with shorter BRFS (HR = 5.52, 95% CI = 2.36 to 12.90; P < .001) who may be considered for intensified monitoring and/or adjuvant therapy.
Conclusions
Compared with previous qualitative approaches, qPTEN improves risk stratification of postradical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery.</description><identifier>ISSN: 0027-8874</identifier><identifier>EISSN: 1460-2105</identifier><identifier>DOI: 10.1093/jnci/djaa032</identifier><identifier>PMID: 32129857</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Cohort Studies ; Confidence intervals ; Editor's Choice ; Hazard assessment ; Health hazards ; Health risks ; Homology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Patients ; Prognosis ; Proportional Hazards Models ; Prostate cancer ; Prostatectomy ; Prostatic Neoplasms - enzymology ; Prostatic Neoplasms - surgery ; PTEN Phosphohydrolase - metabolism ; PTEN protein ; Quantitative analysis ; Retrospective Studies ; Risk Assessment ; Statistical analysis ; Statistical methods ; Statistical tests ; Subpopulations ; Surgery ; Tensin ; Training</subject><ispartof>JNCI : Journal of the National Cancer Institute, 2020-11, Vol.112 (11), p.1098-1104</ispartof><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-3f6f727f7c2f17c8a39bdc2d13a4f505a35eb148c8c788d62bfee5d495b50b343</citedby><cites>FETCH-LOGICAL-c444t-3f6f727f7c2f17c8a39bdc2d13a4f505a35eb148c8c788d62bfee5d495b50b343</cites><orcidid>0000-0002-5889-1905 ; 0000-0001-5985-3698 ; 0000-0001-7391-9788 ; 0000-0002-7741-9868 ; 0000-0001-9369-4264 ; 0000-0002-3693-6412 ; 0000-0001-5836-7700 ; 0000-0002-7268-4494</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1583,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32129857$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jamaspishvili, Tamara</creatorcontrib><creatorcontrib>Patel, Palak G</creatorcontrib><creatorcontrib>Niu, Yi</creatorcontrib><creatorcontrib>Vidotto, Thiago</creatorcontrib><creatorcontrib>Caven, Isabelle</creatorcontrib><creatorcontrib>Livergant, Rachel</creatorcontrib><creatorcontrib>Fu, Winnie</creatorcontrib><creatorcontrib>Kawashima, Atsunari</creatorcontrib><creatorcontrib>How, Nathan</creatorcontrib><creatorcontrib>Okello, John B</creatorcontrib><creatorcontrib>Guedes, Liana B</creatorcontrib><creatorcontrib>Ouellet, Veronique</creatorcontrib><creatorcontrib>Picanço, Clarissa</creatorcontrib><creatorcontrib>Koti, Madhuri</creatorcontrib><creatorcontrib>Reis, Rodolfo B</creatorcontrib><creatorcontrib>Saad, Fred</creatorcontrib><creatorcontrib>Mes-Masson, Anne-Marie</creatorcontrib><creatorcontrib>Lotan, Tamara L</creatorcontrib><creatorcontrib>Squire, Jeremy A</creatorcontrib><creatorcontrib>Peng, Yingwei P</creatorcontrib><creatorcontrib>Siemens, D Robert</creatorcontrib><creatorcontrib>Berman, David M</creatorcontrib><title>Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN)</title><title>JNCI : Journal of the National Cancer Institute</title><addtitle>J Natl Cancer Inst</addtitle><description>Abstract
Background
Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application.
Methods
PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided.
Results
PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.59 to 3.87; P < .001) and validation cohorts (HR = 4.22, 95% CI = 2.01 to 8.83; P < .001). The qPTEN scoring method identified patients who recurred within 5.4 years after surgery (P < .001). In men with favorable risk of biochemical recurrence (Cancer of the Prostate Risk Assessment – Postsurgical scores <5 and no adverse pathological features), qPTEN identified a subset of patients with shorter BRFS (HR = 5.52, 95% CI = 2.36 to 12.90; P < .001) who may be considered for intensified monitoring and/or adjuvant therapy.
Conclusions
Compared with previous qualitative approaches, qPTEN improves risk stratification of postradical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery.</description><subject>Cohort Studies</subject><subject>Confidence intervals</subject><subject>Editor's Choice</subject><subject>Hazard assessment</subject><subject>Health hazards</subject><subject>Health risks</subject><subject>Homology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Prostate cancer</subject><subject>Prostatectomy</subject><subject>Prostatic Neoplasms - enzymology</subject><subject>Prostatic Neoplasms - surgery</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN protein</subject><subject>Quantitative analysis</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Statistical tests</subject><subject>Subpopulations</subject><subject>Surgery</subject><subject>Tensin</subject><subject>Training</subject><issn>0027-8874</issn><issn>1460-2105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9P2zAUxy20CbqO286TpR3WScvqX4mdyyRUdWNSBRuUEwfLcWzqkMbFTpD23-PSgmCHvYOfpffxV9_nLwAfMPqGUUmnTafdtG6UQpQcgBFmBcoIRvkbMEKI8EwIzo7AuxgblKok7BAcUYJJKXI-AtcXLt7Cyz6o3lmn0-k76C38HXzsVW_gTHXaBLhcBT_crOCfQXW9SxN3b-BJjCbGten6xyfL-Rlc-Bjh5G57__IevLWqjeZ438fg6sd8OTvNFuc_f81OFplmjPUZtYXlhFuuicVcC0XLqtakxlQxm6Nc0dxUmAktNBeiLkhljclrVuZVjirK6Bh83-luhmptap38BNXKTXBrFf5Kr5x8PencSt74e8mLoiRkKzDZCwR_N5jYy7WL2rSt6owfoiSUY8wwomVCP_2DNn4IXVpPEsYLLGiBcaK-7iidvjEGY5_NYCS3qcltanKfWsI_vlzgGX6KKQGfd4AfNv-XegCEq6IA</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Jamaspishvili, Tamara</creator><creator>Patel, Palak G</creator><creator>Niu, Yi</creator><creator>Vidotto, Thiago</creator><creator>Caven, Isabelle</creator><creator>Livergant, Rachel</creator><creator>Fu, Winnie</creator><creator>Kawashima, Atsunari</creator><creator>How, Nathan</creator><creator>Okello, John B</creator><creator>Guedes, Liana B</creator><creator>Ouellet, Veronique</creator><creator>Picanço, Clarissa</creator><creator>Koti, Madhuri</creator><creator>Reis, Rodolfo B</creator><creator>Saad, Fred</creator><creator>Mes-Masson, Anne-Marie</creator><creator>Lotan, Tamara L</creator><creator>Squire, Jeremy A</creator><creator>Peng, Yingwei P</creator><creator>Siemens, D Robert</creator><creator>Berman, David M</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5889-1905</orcidid><orcidid>https://orcid.org/0000-0001-5985-3698</orcidid><orcidid>https://orcid.org/0000-0001-7391-9788</orcidid><orcidid>https://orcid.org/0000-0002-7741-9868</orcidid><orcidid>https://orcid.org/0000-0001-9369-4264</orcidid><orcidid>https://orcid.org/0000-0002-3693-6412</orcidid><orcidid>https://orcid.org/0000-0001-5836-7700</orcidid><orcidid>https://orcid.org/0000-0002-7268-4494</orcidid></search><sort><creationdate>20201101</creationdate><title>Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN)</title><author>Jamaspishvili, Tamara ; Patel, Palak G ; Niu, Yi ; Vidotto, Thiago ; Caven, Isabelle ; Livergant, Rachel ; Fu, Winnie ; Kawashima, Atsunari ; How, Nathan ; Okello, John B ; Guedes, Liana B ; Ouellet, Veronique ; Picanço, Clarissa ; Koti, Madhuri ; Reis, Rodolfo B ; Saad, Fred ; Mes-Masson, Anne-Marie ; Lotan, Tamara L ; Squire, Jeremy A ; Peng, Yingwei P ; Siemens, D Robert ; Berman, David M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-3f6f727f7c2f17c8a39bdc2d13a4f505a35eb148c8c788d62bfee5d495b50b343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cohort Studies</topic><topic>Confidence intervals</topic><topic>Editor's Choice</topic><topic>Hazard assessment</topic><topic>Health hazards</topic><topic>Health risks</topic><topic>Homology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Prostate cancer</topic><topic>Prostatectomy</topic><topic>Prostatic Neoplasms - enzymology</topic><topic>Prostatic Neoplasms - surgery</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>PTEN protein</topic><topic>Quantitative analysis</topic><topic>Retrospective Studies</topic><topic>Risk Assessment</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Statistical tests</topic><topic>Subpopulations</topic><topic>Surgery</topic><topic>Tensin</topic><topic>Training</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jamaspishvili, Tamara</creatorcontrib><creatorcontrib>Patel, Palak G</creatorcontrib><creatorcontrib>Niu, Yi</creatorcontrib><creatorcontrib>Vidotto, Thiago</creatorcontrib><creatorcontrib>Caven, Isabelle</creatorcontrib><creatorcontrib>Livergant, Rachel</creatorcontrib><creatorcontrib>Fu, Winnie</creatorcontrib><creatorcontrib>Kawashima, Atsunari</creatorcontrib><creatorcontrib>How, Nathan</creatorcontrib><creatorcontrib>Okello, John B</creatorcontrib><creatorcontrib>Guedes, Liana B</creatorcontrib><creatorcontrib>Ouellet, Veronique</creatorcontrib><creatorcontrib>Picanço, Clarissa</creatorcontrib><creatorcontrib>Koti, Madhuri</creatorcontrib><creatorcontrib>Reis, Rodolfo B</creatorcontrib><creatorcontrib>Saad, Fred</creatorcontrib><creatorcontrib>Mes-Masson, Anne-Marie</creatorcontrib><creatorcontrib>Lotan, Tamara L</creatorcontrib><creatorcontrib>Squire, Jeremy A</creatorcontrib><creatorcontrib>Peng, Yingwei P</creatorcontrib><creatorcontrib>Siemens, D Robert</creatorcontrib><creatorcontrib>Berman, David M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JNCI : Journal of the National Cancer Institute</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jamaspishvili, Tamara</au><au>Patel, Palak G</au><au>Niu, Yi</au><au>Vidotto, Thiago</au><au>Caven, Isabelle</au><au>Livergant, Rachel</au><au>Fu, Winnie</au><au>Kawashima, Atsunari</au><au>How, Nathan</au><au>Okello, John B</au><au>Guedes, Liana B</au><au>Ouellet, Veronique</au><au>Picanço, Clarissa</au><au>Koti, Madhuri</au><au>Reis, Rodolfo B</au><au>Saad, Fred</au><au>Mes-Masson, Anne-Marie</au><au>Lotan, Tamara L</au><au>Squire, Jeremy A</au><au>Peng, Yingwei P</au><au>Siemens, D Robert</au><au>Berman, David M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN)</atitle><jtitle>JNCI : Journal of the National Cancer Institute</jtitle><addtitle>J Natl Cancer Inst</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>112</volume><issue>11</issue><spage>1098</spage><epage>1104</epage><pages>1098-1104</pages><issn>0027-8874</issn><eissn>1460-2105</eissn><abstract>Abstract
Background
Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application.
Methods
PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided.
Results
PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.59 to 3.87; P < .001) and validation cohorts (HR = 4.22, 95% CI = 2.01 to 8.83; P < .001). The qPTEN scoring method identified patients who recurred within 5.4 years after surgery (P < .001). In men with favorable risk of biochemical recurrence (Cancer of the Prostate Risk Assessment – Postsurgical scores <5 and no adverse pathological features), qPTEN identified a subset of patients with shorter BRFS (HR = 5.52, 95% CI = 2.36 to 12.90; P < .001) who may be considered for intensified monitoring and/or adjuvant therapy.
Conclusions
Compared with previous qualitative approaches, qPTEN improves risk stratification of postradical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>32129857</pmid><doi>10.1093/jnci/djaa032</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-5889-1905</orcidid><orcidid>https://orcid.org/0000-0001-5985-3698</orcidid><orcidid>https://orcid.org/0000-0001-7391-9788</orcidid><orcidid>https://orcid.org/0000-0002-7741-9868</orcidid><orcidid>https://orcid.org/0000-0001-9369-4264</orcidid><orcidid>https://orcid.org/0000-0002-3693-6412</orcidid><orcidid>https://orcid.org/0000-0001-5836-7700</orcidid><orcidid>https://orcid.org/0000-0002-7268-4494</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Cohort Studies Confidence intervals Editor's Choice Hazard assessment Health hazards Health risks Homology Humans Immunohistochemistry Kaplan-Meier Estimate Male Patients Prognosis Proportional Hazards Models Prostate cancer Prostatectomy Prostatic Neoplasms - enzymology Prostatic Neoplasms - surgery PTEN Phosphohydrolase - metabolism PTEN protein Quantitative analysis Retrospective Studies Risk Assessment Statistical analysis Statistical methods Statistical tests Subpopulations Surgery Tensin Training |
| title | Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN) |
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