Perineural Invasion and Risk of Lethal Prostate Cancer
Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated with cancer aggressiveness. We investigated the association between PNI and lethal prostate cancer i...
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creator | Zareba, Piotr Flavin, Richard Isikbay, Masis Rider, Jennifer R Gerke, Travis A Finn, Stephen Pettersson, Andreas Giunchi, Francesca Unger, Robert H Tinianow, Alex M Andersson, Swen-Olof Andrén, Ove Fall, Katja Fiorentino, Michelangelo Mucci, Lorelei A |
description | Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated with cancer aggressiveness.
We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.
The prevalence of PNI was 7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer [OR 7.4; 95% confidence interval (CI), 3.6-16.6;
< 0.001]. A positive, although not statistically significant, association persisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1;
= 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3;
=0.04).
These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness.
Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis.
. |
doi_str_mv | 10.1158/1055-9965.EPI-16-0237 |
format | Article |
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We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.
The prevalence of PNI was 7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer [OR 7.4; 95% confidence interval (CI), 3.6-16.6;
< 0.001]. A positive, although not statistically significant, association persisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1;
= 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3;
=0.04).
These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness.
Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis.
.</description><identifier>ISSN: 1055-9965</identifier><identifier>ISSN: 1538-7755</identifier><identifier>EISSN: 1538-7755</identifier><identifier>DOI: 10.1158/1055-9965.EPI-16-0237</identifier><identifier>PMID: 28062398</identifier><language>eng</language><publisher>United States: American Association for Cancer Research, Inc</publisher><subject>Adult ; Aged ; Angiogenesis ; Apoptosis ; Cancer surgery ; Cohort Studies ; Health risks ; Humans ; Male ; Medical personnel ; Metastases ; Metastasis ; Middle Aged ; Neoplasm Grading - methods ; Neoplasm Invasiveness - pathology ; Nerves ; Oncology ; Onkologi ; Peripheral Nerves - pathology ; Prostate cancer ; Prostatectomy ; Prostatic Neoplasms - pathology ; Statistical analysis ; Tumors ; Urological surgery</subject><ispartof>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2017-05, Vol.26 (5), p.719-726</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research, Inc. May 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c665t-b6b8416764768e6e7f94f731a4a562deb214574ee9eadb0048a6887e6aacda3a3</citedby><cites>FETCH-LOGICAL-c665t-b6b8416764768e6e7f94f731a4a562deb214574ee9eadb0048a6887e6aacda3a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28062398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-57864$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:135753550$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Zareba, Piotr</creatorcontrib><creatorcontrib>Flavin, Richard</creatorcontrib><creatorcontrib>Isikbay, Masis</creatorcontrib><creatorcontrib>Rider, Jennifer R</creatorcontrib><creatorcontrib>Gerke, Travis A</creatorcontrib><creatorcontrib>Finn, Stephen</creatorcontrib><creatorcontrib>Pettersson, Andreas</creatorcontrib><creatorcontrib>Giunchi, Francesca</creatorcontrib><creatorcontrib>Unger, Robert H</creatorcontrib><creatorcontrib>Tinianow, Alex M</creatorcontrib><creatorcontrib>Andersson, Swen-Olof</creatorcontrib><creatorcontrib>Andrén, Ove</creatorcontrib><creatorcontrib>Fall, Katja</creatorcontrib><creatorcontrib>Fiorentino, Michelangelo</creatorcontrib><creatorcontrib>Mucci, Lorelei A</creatorcontrib><creatorcontrib>Transdisciplinary Prostate Cancer Partnership (ToPCaP)</creatorcontrib><title>Perineural Invasion and Risk of Lethal Prostate Cancer</title><title>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION</title><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><description>Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated with cancer aggressiveness.
We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.
The prevalence of PNI was 7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer [OR 7.4; 95% confidence interval (CI), 3.6-16.6;
< 0.001]. A positive, although not statistically significant, association persisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1;
= 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3;
=0.04).
These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness.
Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis.
.</description><subject>Adult</subject><subject>Aged</subject><subject>Angiogenesis</subject><subject>Apoptosis</subject><subject>Cancer surgery</subject><subject>Cohort Studies</subject><subject>Health risks</subject><subject>Humans</subject><subject>Male</subject><subject>Medical personnel</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Neoplasm Grading - methods</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>Nerves</subject><subject>Oncology</subject><subject>Onkologi</subject><subject>Peripheral Nerves - pathology</subject><subject>Prostate cancer</subject><subject>Prostatectomy</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Statistical analysis</subject><subject>Tumors</subject><subject>Urological surgery</subject><issn>1055-9965</issn><issn>1538-7755</issn><issn>1538-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqNkt9rFDEQx4Motlb_BGXBFx-6NdlkJsmLUM6qBwceor6G7O5su-3dpia7lf73Zr1rsYLgQ8gw85lhfnwZeyn4iRBg3goOUFqLcHK2XpYCS15J_YgdCpCm1BrgcbbvmAP2LKVLzrm2AE_ZQWU4VtKaQ4Zriv1AU_SbYjnc-NSHofBDW3zp01URumJF40WOrWNIox-pWPihoficPen8JtGL_X_Evn04-7r4VK4-f1wuTldlgwhjWWNtlECNSqMhJN1Z1WkpvPKAVUt1JRRoRWTJtzXnyng0RhN637ReennEyl3d9JOup9pdx37r460Lvnd711W2yClrreSZP_4n_77_fupCPM9vcqANqoy_2-GZ3VLb0DDmRTzIehgZ-gt3Hm4cKCGlhVzgzb5ADD8mSqPb9qmhzcYPFKbkhLFa5oEt_gcKCMZKmNt6_Rd6GaY45EU7YY2swIrfFOyoJt8mReru-xbczRpx8_3dfH-XNeIEulkjOe_Vn0PfZ92JQv4C8yi3vA</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Zareba, Piotr</creator><creator>Flavin, Richard</creator><creator>Isikbay, Masis</creator><creator>Rider, Jennifer R</creator><creator>Gerke, Travis A</creator><creator>Finn, Stephen</creator><creator>Pettersson, Andreas</creator><creator>Giunchi, Francesca</creator><creator>Unger, Robert H</creator><creator>Tinianow, Alex M</creator><creator>Andersson, Swen-Olof</creator><creator>Andrén, Ove</creator><creator>Fall, Katja</creator><creator>Fiorentino, Michelangelo</creator><creator>Mucci, Lorelei A</creator><general>American Association for Cancer Research, Inc</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>7TM</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D91</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20170501</creationdate><title>Perineural Invasion and Risk of Lethal Prostate Cancer</title><author>Zareba, Piotr ; Flavin, Richard ; Isikbay, Masis ; Rider, Jennifer R ; Gerke, Travis A ; Finn, Stephen ; Pettersson, Andreas ; Giunchi, Francesca ; Unger, Robert H ; Tinianow, Alex M ; Andersson, Swen-Olof ; Andrén, Ove ; Fall, Katja ; Fiorentino, Michelangelo ; Mucci, Lorelei A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c665t-b6b8416764768e6e7f94f731a4a562deb214574ee9eadb0048a6887e6aacda3a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Angiogenesis</topic><topic>Apoptosis</topic><topic>Cancer surgery</topic><topic>Cohort Studies</topic><topic>Health risks</topic><topic>Humans</topic><topic>Male</topic><topic>Medical personnel</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Neoplasm Grading - methods</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>Nerves</topic><topic>Oncology</topic><topic>Onkologi</topic><topic>Peripheral Nerves - pathology</topic><topic>Prostate cancer</topic><topic>Prostatectomy</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Statistical analysis</topic><topic>Tumors</topic><topic>Urological surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zareba, Piotr</creatorcontrib><creatorcontrib>Flavin, Richard</creatorcontrib><creatorcontrib>Isikbay, Masis</creatorcontrib><creatorcontrib>Rider, Jennifer R</creatorcontrib><creatorcontrib>Gerke, Travis A</creatorcontrib><creatorcontrib>Finn, Stephen</creatorcontrib><creatorcontrib>Pettersson, Andreas</creatorcontrib><creatorcontrib>Giunchi, Francesca</creatorcontrib><creatorcontrib>Unger, Robert H</creatorcontrib><creatorcontrib>Tinianow, Alex M</creatorcontrib><creatorcontrib>Andersson, Swen-Olof</creatorcontrib><creatorcontrib>Andrén, Ove</creatorcontrib><creatorcontrib>Fall, Katja</creatorcontrib><creatorcontrib>Fiorentino, Michelangelo</creatorcontrib><creatorcontrib>Mucci, Lorelei A</creatorcontrib><creatorcontrib>Transdisciplinary Prostate Cancer Partnership (ToPCaP)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Örebro universitet</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zareba, Piotr</au><au>Flavin, Richard</au><au>Isikbay, Masis</au><au>Rider, Jennifer R</au><au>Gerke, Travis A</au><au>Finn, Stephen</au><au>Pettersson, Andreas</au><au>Giunchi, Francesca</au><au>Unger, Robert H</au><au>Tinianow, Alex M</au><au>Andersson, Swen-Olof</au><au>Andrén, Ove</au><au>Fall, Katja</au><au>Fiorentino, Michelangelo</au><au>Mucci, Lorelei A</au><aucorp>Transdisciplinary Prostate Cancer Partnership (ToPCaP)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perineural Invasion and Risk of Lethal Prostate Cancer</atitle><jtitle>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION</jtitle><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>26</volume><issue>5</issue><spage>719</spage><epage>726</epage><pages>719-726</pages><issn>1055-9965</issn><issn>1538-7755</issn><eissn>1538-7755</eissn><abstract>Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated with cancer aggressiveness.
We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.
The prevalence of PNI was 7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer [OR 7.4; 95% confidence interval (CI), 3.6-16.6;
< 0.001]. A positive, although not statistically significant, association persisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1;
= 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3;
=0.04).
These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness.
Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research, Inc</pub><pmid>28062398</pmid><doi>10.1158/1055-9965.EPI-16-0237</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online |
subjects | Adult Aged Angiogenesis Apoptosis Cancer surgery Cohort Studies Health risks Humans Male Medical personnel Metastases Metastasis Middle Aged Neoplasm Grading - methods Neoplasm Invasiveness - pathology Nerves Oncology Onkologi Peripheral Nerves - pathology Prostate cancer Prostatectomy Prostatic Neoplasms - pathology Statistical analysis Tumors Urological surgery |
title | Perineural Invasion and Risk of Lethal Prostate Cancer |
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