A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer
PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, predominantly surgically treated cohort. In the Health Professionals Follow-up Study and Physicians�...
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| creator | Ahearn, Thomas U Pettersson, Andreas Ebot, Ericka M Gerke, Travis Graff, Rebecca E Morais, Carlos L Hicks, Jessica L Wilson, Kathryn M Rider, Jennifer R Sesso, Howard D Fiorentino, Michelangelo Flavin, Richard Finn, Stephen Giovannucci, Edward L Loda, Massimo Stampfer, Meir J De Marzo, Angelo M Mucci, Lorelei A Lotan, Tamara L |
| description | PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, predominantly surgically treated cohort.
In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided.
On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors.
PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer. |
| doi_str_mv | 10.1093/jnci/djv346 |
| format | Article |
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In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided.
On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors.
PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer.</description><identifier>ISSN: 0027-8874</identifier><identifier>EISSN: 1460-2105</identifier><identifier>DOI: 10.1093/jnci/djv346</identifier><identifier>PMID: 26615022</identifier><identifier>CODEN: JNCIEQ</identifier><language>eng</language><publisher>United States: Oxford Publishing Limited (England)</publisher><subject>Age Factors ; Aged ; Biomarkers ; Biomarkers, Tumor - analysis ; Body Mass Index ; Confidence intervals ; Disease Progression ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Genes ; Health Personnel - statistics & numerical data ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Oncogene Proteins, Fusion - analysis ; Physicians - statistics & numerical data ; Proportional Hazards Models ; Prospective Studies ; Prostate cancer ; Prostatic Neoplasms - chemistry ; Prostatic Neoplasms - mortality ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - surgery ; PTEN Phosphohydrolase - analysis ; Risk Assessment ; Serine Endopeptidases - analysis ; Trans-Activators - analysis ; Transcriptional Regulator ERG ; Tumor Suppressor Proteins - analysis ; Tumors ; United States - epidemiology</subject><ispartof>JNCI : Journal of the National Cancer Institute, 2016-02, Vol.108 (2), p.djv346</ispartof><rights>The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Copyright Oxford Publishing Limited(England) Feb 2016</rights><rights>The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-e1d760c5a0067c4959624e4e65847ce8d8b0bb177b79da5e571c1c2a47ea5f483</citedby><cites>FETCH-LOGICAL-c513t-e1d760c5a0067c4959624e4e65847ce8d8b0bb177b79da5e571c1c2a47ea5f483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26615022$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:133049982$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahearn, Thomas U</creatorcontrib><creatorcontrib>Pettersson, Andreas</creatorcontrib><creatorcontrib>Ebot, Ericka M</creatorcontrib><creatorcontrib>Gerke, Travis</creatorcontrib><creatorcontrib>Graff, Rebecca E</creatorcontrib><creatorcontrib>Morais, Carlos L</creatorcontrib><creatorcontrib>Hicks, Jessica L</creatorcontrib><creatorcontrib>Wilson, Kathryn M</creatorcontrib><creatorcontrib>Rider, Jennifer R</creatorcontrib><creatorcontrib>Sesso, Howard D</creatorcontrib><creatorcontrib>Fiorentino, Michelangelo</creatorcontrib><creatorcontrib>Flavin, Richard</creatorcontrib><creatorcontrib>Finn, Stephen</creatorcontrib><creatorcontrib>Giovannucci, Edward L</creatorcontrib><creatorcontrib>Loda, Massimo</creatorcontrib><creatorcontrib>Stampfer, Meir J</creatorcontrib><creatorcontrib>De Marzo, Angelo M</creatorcontrib><creatorcontrib>Mucci, Lorelei A</creatorcontrib><creatorcontrib>Lotan, Tamara L</creatorcontrib><title>A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer</title><title>JNCI : Journal of the National Cancer Institute</title><addtitle>J Natl Cancer Inst</addtitle><description>PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, predominantly surgically treated cohort.
In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided.
On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors.
PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer.</description><subject>Age Factors</subject><subject>Aged</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Body Mass Index</subject><subject>Confidence intervals</subject><subject>Disease Progression</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Health Personnel - statistics & numerical data</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Odds Ratio</subject><subject>Oncogene Proteins, Fusion - analysis</subject><subject>Physicians - statistics & numerical data</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - chemistry</subject><subject>Prostatic Neoplasms - mortality</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - surgery</subject><subject>PTEN Phosphohydrolase - analysis</subject><subject>Risk Assessment</subject><subject>Serine Endopeptidases - analysis</subject><subject>Trans-Activators - analysis</subject><subject>Transcriptional Regulator ERG</subject><subject>Tumor Suppressor Proteins - analysis</subject><subject>Tumors</subject><subject>United States - epidemiology</subject><issn>0027-8874</issn><issn>1460-2105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNpdkd9rUzEcxYM4XJ0--S4BXwS5W5Kbny_CKHUOig7ZnkNu7rdb6m1Sk9u6_femax3OvCTkfHL45hyE3lFySolpz5bRh7N-uW25fIEmlEvSMErESzQhhKlGa8WP0etSlqQuw_grdMykpIIwNkE35_gqp7IGP4Yt4Mu4hTKGWzeGFHFa4Kvr2Tc8T6VgF3s8-3GBZ_frDKXs9BDxHMY7Nzx6jG4EPHXRQ36DjhZuKPD2sJ-gmy-z6-nXZv794nJ6Pm-8oO3YAO2VJF44QqTy3AgjGQcOUmiuPOhed6TrqFKdMr0TIBT11DPHFTix4Lo9Qc3et_yG9aaz6xxWLj_Y5II9XP2sJ7CCaGNE5T_v-aqsoPcQx-yGZ8-eKzHc2du0tVzXyVpZDT4eDHL6talR2VUoHobBRUibYqlqNddMGVPRD_-hy7TJscZRKakN4e3jDz7tKV8TLBkWT8NQYnf12l29dl9vpd__O_8T-7fP9g9swqHz</recordid><startdate>20160201</startdate><enddate>20160201</enddate><creator>Ahearn, Thomas U</creator><creator>Pettersson, Andreas</creator><creator>Ebot, Ericka M</creator><creator>Gerke, Travis</creator><creator>Graff, Rebecca E</creator><creator>Morais, Carlos L</creator><creator>Hicks, Jessica L</creator><creator>Wilson, Kathryn M</creator><creator>Rider, Jennifer R</creator><creator>Sesso, Howard D</creator><creator>Fiorentino, Michelangelo</creator><creator>Flavin, Richard</creator><creator>Finn, Stephen</creator><creator>Giovannucci, Edward L</creator><creator>Loda, Massimo</creator><creator>Stampfer, Meir J</creator><creator>De Marzo, Angelo M</creator><creator>Mucci, Lorelei A</creator><creator>Lotan, Tamara L</creator><general>Oxford Publishing Limited (England)</general><general>Oxford University Press</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><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20160201</creationdate><title>A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer</title><author>Ahearn, Thomas U ; Pettersson, Andreas ; Ebot, Ericka M ; Gerke, Travis ; Graff, Rebecca E ; Morais, Carlos L ; Hicks, Jessica L ; Wilson, Kathryn M ; Rider, Jennifer R ; Sesso, Howard D ; Fiorentino, Michelangelo ; Flavin, Richard ; Finn, Stephen ; Giovannucci, Edward L ; Loda, Massimo ; Stampfer, Meir J ; De Marzo, Angelo M ; Mucci, Lorelei A ; Lotan, Tamara L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-e1d760c5a0067c4959624e4e65847ce8d8b0bb177b79da5e571c1c2a47ea5f483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Age Factors</topic><topic>Aged</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Body Mass Index</topic><topic>Confidence intervals</topic><topic>Disease Progression</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Health Personnel - statistics & numerical data</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Staging</topic><topic>Odds Ratio</topic><topic>Oncogene Proteins, Fusion - analysis</topic><topic>Physicians - statistics & numerical data</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - chemistry</topic><topic>Prostatic Neoplasms - mortality</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - surgery</topic><topic>PTEN Phosphohydrolase - analysis</topic><topic>Risk Assessment</topic><topic>Serine Endopeptidases - analysis</topic><topic>Trans-Activators - analysis</topic><topic>Transcriptional Regulator ERG</topic><topic>Tumor Suppressor Proteins - analysis</topic><topic>Tumors</topic><topic>United States - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahearn, Thomas U</creatorcontrib><creatorcontrib>Pettersson, Andreas</creatorcontrib><creatorcontrib>Ebot, Ericka M</creatorcontrib><creatorcontrib>Gerke, Travis</creatorcontrib><creatorcontrib>Graff, Rebecca E</creatorcontrib><creatorcontrib>Morais, Carlos L</creatorcontrib><creatorcontrib>Hicks, Jessica L</creatorcontrib><creatorcontrib>Wilson, Kathryn M</creatorcontrib><creatorcontrib>Rider, Jennifer R</creatorcontrib><creatorcontrib>Sesso, Howard D</creatorcontrib><creatorcontrib>Fiorentino, Michelangelo</creatorcontrib><creatorcontrib>Flavin, Richard</creatorcontrib><creatorcontrib>Finn, Stephen</creatorcontrib><creatorcontrib>Giovannucci, Edward L</creatorcontrib><creatorcontrib>Loda, Massimo</creatorcontrib><creatorcontrib>Stampfer, Meir J</creatorcontrib><creatorcontrib>De Marzo, Angelo M</creatorcontrib><creatorcontrib>Mucci, Lorelei A</creatorcontrib><creatorcontrib>Lotan, Tamara L</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 - 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However, the association of PTEN loss with lethal disease has not been tested in a large, predominantly surgically treated cohort.
In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided.
On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors.
PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer.</abstract><cop>United States</cop><pub>Oxford Publishing Limited (England)</pub><pmid>26615022</pmid><doi>10.1093/jnci/djv346</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | JNCI : Journal of the National Cancer Institute, 2016-02, Vol.108 (2), p.djv346 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; SWEPUB Freely available online |
| subjects | Age Factors Aged Biomarkers Biomarkers, Tumor - analysis Body Mass Index Confidence intervals Disease Progression Follow-Up Studies Gene Expression Regulation, Neoplastic Genes Health Personnel - statistics & numerical data Humans Immunohistochemistry Kaplan-Meier Estimate Male Neoplasm Grading Neoplasm Staging Odds Ratio Oncogene Proteins, Fusion - analysis Physicians - statistics & numerical data Proportional Hazards Models Prospective Studies Prostate cancer Prostatic Neoplasms - chemistry Prostatic Neoplasms - mortality Prostatic Neoplasms - pathology Prostatic Neoplasms - surgery PTEN Phosphohydrolase - analysis Risk Assessment Serine Endopeptidases - analysis Trans-Activators - analysis Transcriptional Regulator ERG Tumor Suppressor Proteins - analysis Tumors United States - epidemiology |
| title | A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer |
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