DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance
Background Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients. Methods We assessed DNA ploidy by imag...
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| Veröffentlicht in: | British journal of cancer 2024-09, Vol.131 (5), p.895-904 |
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| creator | Cyll, Karolina Skaaheim Haug, Erik Pradhan, Manohar Vlatkovic, Ljiljana Carlsen, Birgitte Löffeler, Sven Kildal, Wanja Skogstad, Karin Hauge Torkelsen, Frida Syvertsen, Rolf Anders Askautrud, Hanne A. Liestøl, Knut Kleppe, Andreas Danielsen, Håvard E. |
| description | Background
Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients.
Methods
We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint.
Results
The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (
p
|
| doi_str_mv | 10.1038/s41416-024-02780-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_3HK</sourceid><recordid>TN_cdi_cristin_nora_10037_34865</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3075702215</sourcerecordid><originalsourceid>FETCH-LOGICAL-c380t-9b0bd5f8477753357bd310ddbd5119320a8693b0403fae5d2dd427905a42f85b3</originalsourceid><addsrcrecordid>eNp9kctu1DAUhi0EokPhBViApW7YBI7tJLZXqCrlIlWFRVlbTuwElxl7sJNR5-05YdpyWbCwLPt8_7n9hDxn8JqBUG9KzWrWVsBrPFJBdfOArFgjeMUUlw_JCgBkBZrDEXlSyjU-NSj5mBwJpVvGNF-R_bvLU7pdp-D21EZHv1ydX1JbaBfSxubvPhc6pEy32bvQTyGO1I5j9qWEnacuFG-LpyEikMpkJ097G3uPAjsFH6dC5-jwaVGLgjLnnQ_r9cI8JY8Guy7-2e19TL6-P786-1hdfP7w6ez0ouqFgqnSHXSuGVQtpWyEaGTnBAPn8BMnEBysarXooAYxWN847lzNpYbG1nxQTSeOydtD3u3cbbzrsats12abAw64N8kG83ckhm9mTDvDmGiV5g1meHnI0OdQcAcmpmwNAxDSiFq1C_HqtkZOP2ZfJrMJpffLoD7NxQiQjQTO2YKe_INepzlH3ABSWuu61VIixe9KplKyH-77ZWAW883BfIPmm1_mmxsUvfhz0nvJndsIiANQMBRHn3_X_k_an8SsuvM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3099946977</pqid></control><display><type>article</type><title>DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance</title><source>NORA - Norwegian Open Research Archives</source><creator>Cyll, Karolina ; Skaaheim Haug, Erik ; Pradhan, Manohar ; Vlatkovic, Ljiljana ; Carlsen, Birgitte ; Löffeler, Sven ; Kildal, Wanja ; Skogstad, Karin ; Hauge Torkelsen, Frida ; Syvertsen, Rolf Anders ; Askautrud, Hanne A. ; Liestøl, Knut ; Kleppe, Andreas ; Danielsen, Håvard E.</creator><creatorcontrib>Cyll, Karolina ; Skaaheim Haug, Erik ; Pradhan, Manohar ; Vlatkovic, Ljiljana ; Carlsen, Birgitte ; Löffeler, Sven ; Kildal, Wanja ; Skogstad, Karin ; Hauge Torkelsen, Frida ; Syvertsen, Rolf Anders ; Askautrud, Hanne A. ; Liestøl, Knut ; Kleppe, Andreas ; Danielsen, Håvard E.</creatorcontrib><description>Background
Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients.
Methods
We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint.
Results
The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (
p
< 0.0001) and 1.94 (
p
< 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025;
p
= 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01;
p
= 0.027).
Conclusions
DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol.</description><identifier>ISSN: 0007-0920</identifier><identifier>ISSN: 1532-1827</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-024-02780-x</identifier><identifier>PMID: 38961192</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/211 ; 631/67/1857 ; 631/67/2329 ; 692/4028/67/1244 ; 692/4028/67/589/466 ; Aged ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Deoxyribonucleic acid ; DNA ; DNA, Neoplasm - genetics ; Drug Resistance ; Epidemiology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Molecular Medicine ; Oncology ; Patients ; Ploidies ; Ploidy ; Prognosis ; Prostate cancer ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; PTEN Phosphohydrolase - genetics ; PTEN protein ; Risk assessment ; Surveillance ; Tumors ; Watchful Waiting</subject><ispartof>British journal of cancer, 2024-09, Vol.131 (5), p.895-904</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c380t-9b0bd5f8477753357bd310ddbd5119320a8693b0403fae5d2dd427905a42f85b3</cites><orcidid>0000-0002-3553-2491 ; 0000-0002-8370-5289 ; 0000-0001-6743-0724</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,782,887,26574</link.rule.ids><linktorsrc>$$Uhttp://hdl.handle.net/10037/34865$$EView_record_in_NORA$$FView_record_in_$$GNORA$$Hfree_for_read</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38961192$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cyll, Karolina</creatorcontrib><creatorcontrib>Skaaheim Haug, Erik</creatorcontrib><creatorcontrib>Pradhan, Manohar</creatorcontrib><creatorcontrib>Vlatkovic, Ljiljana</creatorcontrib><creatorcontrib>Carlsen, Birgitte</creatorcontrib><creatorcontrib>Löffeler, Sven</creatorcontrib><creatorcontrib>Kildal, Wanja</creatorcontrib><creatorcontrib>Skogstad, Karin</creatorcontrib><creatorcontrib>Hauge Torkelsen, Frida</creatorcontrib><creatorcontrib>Syvertsen, Rolf Anders</creatorcontrib><creatorcontrib>Askautrud, Hanne A.</creatorcontrib><creatorcontrib>Liestøl, Knut</creatorcontrib><creatorcontrib>Kleppe, Andreas</creatorcontrib><creatorcontrib>Danielsen, Håvard E.</creatorcontrib><title>DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients.
Methods
We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint.
Results
The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (
p
< 0.0001) and 1.94 (
p
< 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025;
p
= 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01;
p
= 0.027).
Conclusions
DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol.</description><subject>631/208/211</subject><subject>631/67/1857</subject><subject>631/67/2329</subject><subject>692/4028/67/1244</subject><subject>692/4028/67/589/466</subject><subject>Aged</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Neoplasm - genetics</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Patients</subject><subject>Ploidies</subject><subject>Ploidy</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN protein</subject><subject>Risk assessment</subject><subject>Surveillance</subject><subject>Tumors</subject><subject>Watchful Waiting</subject><issn>0007-0920</issn><issn>1532-1827</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>3HK</sourceid><recordid>eNp9kctu1DAUhi0EokPhBViApW7YBI7tJLZXqCrlIlWFRVlbTuwElxl7sJNR5-05YdpyWbCwLPt8_7n9hDxn8JqBUG9KzWrWVsBrPFJBdfOArFgjeMUUlw_JCgBkBZrDEXlSyjU-NSj5mBwJpVvGNF-R_bvLU7pdp-D21EZHv1ydX1JbaBfSxubvPhc6pEy32bvQTyGO1I5j9qWEnacuFG-LpyEikMpkJ097G3uPAjsFH6dC5-jwaVGLgjLnnQ_r9cI8JY8Guy7-2e19TL6-P786-1hdfP7w6ez0ouqFgqnSHXSuGVQtpWyEaGTnBAPn8BMnEBysarXooAYxWN847lzNpYbG1nxQTSeOydtD3u3cbbzrsats12abAw64N8kG83ckhm9mTDvDmGiV5g1meHnI0OdQcAcmpmwNAxDSiFq1C_HqtkZOP2ZfJrMJpffLoD7NxQiQjQTO2YKe_INepzlH3ABSWuu61VIixe9KplKyH-77ZWAW883BfIPmm1_mmxsUvfhz0nvJndsIiANQMBRHn3_X_k_an8SsuvM</recordid><startdate>202409</startdate><enddate>202409</enddate><creator>Cyll, Karolina</creator><creator>Skaaheim Haug, Erik</creator><creator>Pradhan, Manohar</creator><creator>Vlatkovic, Ljiljana</creator><creator>Carlsen, Birgitte</creator><creator>Löffeler, Sven</creator><creator>Kildal, Wanja</creator><creator>Skogstad, Karin</creator><creator>Hauge Torkelsen, Frida</creator><creator>Syvertsen, Rolf Anders</creator><creator>Askautrud, Hanne A.</creator><creator>Liestøl, Knut</creator><creator>Kleppe, Andreas</creator><creator>Danielsen, Håvard E.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Springer Nature</general><scope>C6C</scope><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>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>3HK</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3553-2491</orcidid><orcidid>https://orcid.org/0000-0002-8370-5289</orcidid><orcidid>https://orcid.org/0000-0001-6743-0724</orcidid></search><sort><creationdate>202409</creationdate><title>DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance</title><author>Cyll, Karolina ; Skaaheim Haug, Erik ; Pradhan, Manohar ; Vlatkovic, Ljiljana ; Carlsen, Birgitte ; Löffeler, Sven ; Kildal, Wanja ; Skogstad, Karin ; Hauge Torkelsen, Frida ; Syvertsen, Rolf Anders ; Askautrud, Hanne A. ; Liestøl, Knut ; Kleppe, Andreas ; Danielsen, Håvard E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-9b0bd5f8477753357bd310ddbd5119320a8693b0403fae5d2dd427905a42f85b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>631/208/211</topic><topic>631/67/1857</topic><topic>631/67/2329</topic><topic>692/4028/67/1244</topic><topic>692/4028/67/589/466</topic><topic>Aged</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Neoplasm - genetics</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Patients</topic><topic>Ploidies</topic><topic>Ploidy</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>PTEN protein</topic><topic>Risk assessment</topic><topic>Surveillance</topic><topic>Tumors</topic><topic>Watchful Waiting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cyll, Karolina</creatorcontrib><creatorcontrib>Skaaheim Haug, Erik</creatorcontrib><creatorcontrib>Pradhan, Manohar</creatorcontrib><creatorcontrib>Vlatkovic, Ljiljana</creatorcontrib><creatorcontrib>Carlsen, Birgitte</creatorcontrib><creatorcontrib>Löffeler, Sven</creatorcontrib><creatorcontrib>Kildal, Wanja</creatorcontrib><creatorcontrib>Skogstad, Karin</creatorcontrib><creatorcontrib>Hauge Torkelsen, Frida</creatorcontrib><creatorcontrib>Syvertsen, Rolf Anders</creatorcontrib><creatorcontrib>Askautrud, Hanne A.</creatorcontrib><creatorcontrib>Liestøl, Knut</creatorcontrib><creatorcontrib>Kleppe, Andreas</creatorcontrib><creatorcontrib>Danielsen, Håvard E.</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><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>Virology and AIDS Abstracts</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>NORA - Norwegian Open Research Archives</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Cyll, Karolina</au><au>Skaaheim Haug, Erik</au><au>Pradhan, Manohar</au><au>Vlatkovic, Ljiljana</au><au>Carlsen, Birgitte</au><au>Löffeler, Sven</au><au>Kildal, Wanja</au><au>Skogstad, Karin</au><au>Hauge Torkelsen, Frida</au><au>Syvertsen, Rolf Anders</au><au>Askautrud, Hanne A.</au><au>Liestøl, Knut</au><au>Kleppe, Andreas</au><au>Danielsen, Håvard E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2024-09</date><risdate>2024</risdate><volume>131</volume><issue>5</issue><spage>895</spage><epage>904</epage><pages>895-904</pages><issn>0007-0920</issn><issn>1532-1827</issn><eissn>1532-1827</eissn><abstract>Background
Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients.
Methods
We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint.
Results
The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (
p
< 0.0001) and 1.94 (
p
< 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025;
p
= 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01;
p
= 0.027).
Conclusions
DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>38961192</pmid><doi>10.1038/s41416-024-02780-x</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3553-2491</orcidid><orcidid>https://orcid.org/0000-0002-8370-5289</orcidid><orcidid>https://orcid.org/0000-0001-6743-0724</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2024-09, Vol.131 (5), p.895-904 |
| issn | 0007-0920 1532-1827 1532-1827 |
| language | eng |
| recordid | cdi_cristin_nora_10037_34865 |
| source | NORA - Norwegian Open Research Archives |
| subjects | 631/208/211 631/67/1857 631/67/2329 692/4028/67/1244 692/4028/67/589/466 Aged Biomarkers Biomarkers, Tumor - genetics Biomedical and Life Sciences Biomedicine Cancer Research Deoxyribonucleic acid DNA DNA, Neoplasm - genetics Drug Resistance Epidemiology Humans Immunohistochemistry Male Middle Aged Molecular Medicine Oncology Patients Ploidies Ploidy Prognosis Prostate cancer Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology PTEN Phosphohydrolase - genetics PTEN protein Risk assessment Surveillance Tumors Watchful Waiting |
| title | DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance |
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