The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy
Abstract Background Pancreatic ductal adenocarcinoma (PDA) is comprised of a prominent desmoplastic stromal compartment and only 10–40% of the tumour consists of PDA cells. However, how stromal components should be assessed and how the characteristics of the stromal compartment determine clinical ou...
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| creator | Bever, Katherine M Sugar, Elizabeth A Bigelow, Elaine Sharma, Rajni Laheru, Daniel Wolfgang, Christopher L Jaffee, Elizabeth M Anders, Robert A De Jesus-Acosta, Ana Zheng, Lei |
| description | Abstract Background Pancreatic ductal adenocarcinoma (PDA) is comprised of a prominent desmoplastic stromal compartment and only 10–40% of the tumour consists of PDA cells. However, how stromal components should be assessed and how the characteristics of the stromal compartment determine clinical outcomes in PDA patients remain unknown. Method A cohort of 66 consecutive patients who underwent pancreaticoduodenectomy and were primarily followed at Johns Hopkins Hospital between 1998 and 2004, and treated with adjuvant therapy, were included in a retrospective analysis. Resected PDA blocks with good tissue preservation were available for all patients. A new, computer-aided, quantitative method was developed to assess the density and activity of stroma in PDAs and the associations of these characteristics with clinical outcomes. Results High stromal density in resected PDA was found to be significantly associated with longer disease-free [adjusted hazard ratio (aHR) 0.39; P = 0.001] and overall (aHR 0.44; P = 0.004) survival after adjusting for the use of pancreatic cancer vaccine therapy, as well as gender and resection margin positivity. Stromal activity, representing activated pancreatic stellate cells in PDAs, was not significantly associated with the prognosis of resected PDAs. Conclusions These results illustrate the complexity of the role of stroma in PDAs. Further exploration of the prognostic ability of the characteristics of stroma is warranted. |
| doi_str_mv | 10.1111/hpb.12334 |
| format | Article |
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However, how stromal components should be assessed and how the characteristics of the stromal compartment determine clinical outcomes in PDA patients remain unknown. Method A cohort of 66 consecutive patients who underwent pancreaticoduodenectomy and were primarily followed at Johns Hopkins Hospital between 1998 and 2004, and treated with adjuvant therapy, were included in a retrospective analysis. Resected PDA blocks with good tissue preservation were available for all patients. A new, computer-aided, quantitative method was developed to assess the density and activity of stroma in PDAs and the associations of these characteristics with clinical outcomes. Results High stromal density in resected PDA was found to be significantly associated with longer disease-free [adjusted hazard ratio (aHR) 0.39; P = 0.001] and overall (aHR 0.44; P = 0.004) survival after adjusting for the use of pancreatic cancer vaccine therapy, as well as gender and resection margin positivity. Stromal activity, representing activated pancreatic stellate cells in PDAs, was not significantly associated with the prognosis of resected PDAs. Conclusions These results illustrate the complexity of the role of stroma in PDAs. Further exploration of the prognostic ability of the characteristics of stroma is warranted.</description><identifier>ISSN: 1365-182X</identifier><identifier>EISSN: 1477-2574</identifier><identifier>DOI: 10.1111/hpb.12334</identifier><identifier>PMID: 25250696</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Actins - analysis ; Adult ; Aged ; Aged, 80 and over ; Baltimore ; Biomarkers, Tumor - analysis ; Carcinoma, Pancreatic Ductal - chemistry ; Carcinoma, Pancreatic Ductal - mortality ; Carcinoma, Pancreatic Ductal - pathology ; Carcinoma, Pancreatic Ductal - therapy ; Chemoradiotherapy, Adjuvant ; Clinical outcomes ; Collagen - analysis ; Disease-Free Survival ; Female ; Gastroenterology and Hepatology ; Humans ; Image Interpretation, Computer-Assisted ; Immunohistochemistry ; Kaplan-Meier Estimate ; Keratins - analysis ; Male ; Medical prognosis ; Medical research ; Middle Aged ; Neoplasm, Residual ; Original ; Pancreatic cancer ; Pancreatic Neoplasms - chemistry ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - therapy ; Pancreaticoduodenectomy ; Predictive Value of Tests ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stromal Cells - chemistry ; Stromal Cells - pathology ; Time Factors ; Treatment Outcome</subject><ispartof>HPB (Oxford, England), 2015-04, Vol.17 (4), p.292-298</ispartof><rights>International Hepato-Pancreato-Biliary Association</rights><rights>2014 International Hepato-Pancreato-Biliary Association</rights><rights>2014 International Hepato‐Pancreato‐Biliary Association</rights><rights>2014 International Hepato-Pancreato-Biliary Association.</rights><rights>Copyright © 2015 International Hepato-Pancreato-Biliary Association</rights><rights>2014 International Hepato-Pancreato-Biliary Association 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6084-f41dd9f8bb36a4d104c105c208514bc9f21420475fc37f99d7d4d8c58e98be3</citedby><cites>FETCH-LOGICAL-c6084-f41dd9f8bb36a4d104c105c208514bc9f21420475fc37f99d7d4d8c58e98be3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368391/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368391/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,27924,27925,45574,45575,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25250696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bever, Katherine M</creatorcontrib><creatorcontrib>Sugar, Elizabeth A</creatorcontrib><creatorcontrib>Bigelow, Elaine</creatorcontrib><creatorcontrib>Sharma, Rajni</creatorcontrib><creatorcontrib>Laheru, Daniel</creatorcontrib><creatorcontrib>Wolfgang, Christopher L</creatorcontrib><creatorcontrib>Jaffee, Elizabeth M</creatorcontrib><creatorcontrib>Anders, Robert A</creatorcontrib><creatorcontrib>De Jesus-Acosta, Ana</creatorcontrib><creatorcontrib>Zheng, Lei</creatorcontrib><title>The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy</title><title>HPB (Oxford, England)</title><addtitle>HPB (Oxford)</addtitle><description>Abstract Background Pancreatic ductal adenocarcinoma (PDA) is comprised of a prominent desmoplastic stromal compartment and only 10–40% of the tumour consists of PDA cells. However, how stromal components should be assessed and how the characteristics of the stromal compartment determine clinical outcomes in PDA patients remain unknown. Method A cohort of 66 consecutive patients who underwent pancreaticoduodenectomy and were primarily followed at Johns Hopkins Hospital between 1998 and 2004, and treated with adjuvant therapy, were included in a retrospective analysis. Resected PDA blocks with good tissue preservation were available for all patients. A new, computer-aided, quantitative method was developed to assess the density and activity of stroma in PDAs and the associations of these characteristics with clinical outcomes. Results High stromal density in resected PDA was found to be significantly associated with longer disease-free [adjusted hazard ratio (aHR) 0.39; P = 0.001] and overall (aHR 0.44; P = 0.004) survival after adjusting for the use of pancreatic cancer vaccine therapy, as well as gender and resection margin positivity. Stromal activity, representing activated pancreatic stellate cells in PDAs, was not significantly associated with the prognosis of resected PDAs. Conclusions These results illustrate the complexity of the role of stroma in PDAs. Further exploration of the prognostic ability of the characteristics of stroma is warranted.</description><subject>Actins - analysis</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Baltimore</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Carcinoma, Pancreatic Ductal - chemistry</subject><subject>Carcinoma, Pancreatic Ductal - mortality</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Carcinoma, Pancreatic Ductal - therapy</subject><subject>Chemoradiotherapy, Adjuvant</subject><subject>Clinical outcomes</subject><subject>Collagen - analysis</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Gastroenterology and Hepatology</subject><subject>Humans</subject><subject>Image Interpretation, Computer-Assisted</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Keratins - analysis</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Neoplasm, Residual</subject><subject>Original</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - chemistry</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>Pancreaticoduodenectomy</subject><subject>Predictive Value of Tests</subject><subject>Proportional Hazards Models</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Stromal Cells - chemistry</subject><subject>Stromal Cells - pathology</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><issn>1365-182X</issn><issn>1477-2574</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kk1v1DAQhiMEoh9w4A-gSFzoIa2_E18qQQUUqRJI7QFxsRx7suslawc7WbT_Hoe0BSrwxSPPM69m_E5RvMDoFOdzth7aU0woZY-KQ8zquiK8Zo9zTAWvcEO-HBRHKW0QIhhh-bQ4IJxwJKQ4LL7erKEcYlj5kEZnyp3uJyhDV6Yxhq0unS8H7U0EPWdNDiEuj6MDP6YyggG3c35VaruZdtqP5biGqIf9s-JJp_sEz2_v4-L6_bubi8vq6tOHjxdvriojUMOqjmFrZde0LRWaWYyYwYgbghqOWWtkRzAjiNW8M7TupLS1ZbYxvAHZtECPi_NFdZjaLViTm4q6V0N0Wx33Kmin_s54t1arsFOMioZKnAVe3wrE8H2CNKqtSwb6XnsIU1JYCCJog7DI6KsH6CZM0efhZgpzzmU9UycLZWJIKUJ33wxGavZLZb_UL78y-_LP7u_JO4MycLYAP1wP-_8rqcvPb-8k6VIB-c93DqJKJltlwLrs1ahscP9s5PxBlemdd0b332AP6fecKhGF1PW8WvNmYU4xkUjSn_4-xuk</recordid><startdate>201504</startdate><enddate>201504</enddate><creator>Bever, Katherine M</creator><creator>Sugar, Elizabeth A</creator><creator>Bigelow, Elaine</creator><creator>Sharma, Rajni</creator><creator>Laheru, Daniel</creator><creator>Wolfgang, Christopher L</creator><creator>Jaffee, Elizabeth M</creator><creator>Anders, Robert A</creator><creator>De Jesus-Acosta, Ana</creator><creator>Zheng, Lei</creator><general>Elsevier Ltd</general><general>Wiley Subscription Services, Inc</general><general>BlackWell Publishing Ltd</general><scope>6I.</scope><scope>AAFTH</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>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201504</creationdate><title>The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy</title><author>Bever, Katherine M ; Sugar, Elizabeth A ; Bigelow, Elaine ; Sharma, Rajni ; Laheru, Daniel ; Wolfgang, Christopher L ; Jaffee, Elizabeth M ; Anders, Robert A ; De Jesus-Acosta, Ana ; Zheng, Lei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6084-f41dd9f8bb36a4d104c105c208514bc9f21420475fc37f99d7d4d8c58e98be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Actins - analysis</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Baltimore</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Carcinoma, Pancreatic Ductal - chemistry</topic><topic>Carcinoma, Pancreatic Ductal - mortality</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Carcinoma, Pancreatic Ductal - therapy</topic><topic>Chemoradiotherapy, Adjuvant</topic><topic>Clinical outcomes</topic><topic>Collagen - analysis</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Gastroenterology and Hepatology</topic><topic>Humans</topic><topic>Image Interpretation, Computer-Assisted</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Keratins - analysis</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Middle Aged</topic><topic>Neoplasm, Residual</topic><topic>Original</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - chemistry</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pancreatic Neoplasms - therapy</topic><topic>Pancreaticoduodenectomy</topic><topic>Predictive Value of Tests</topic><topic>Proportional Hazards Models</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>Stromal Cells - chemistry</topic><topic>Stromal Cells - pathology</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bever, Katherine M</creatorcontrib><creatorcontrib>Sugar, Elizabeth A</creatorcontrib><creatorcontrib>Bigelow, Elaine</creatorcontrib><creatorcontrib>Sharma, Rajni</creatorcontrib><creatorcontrib>Laheru, Daniel</creatorcontrib><creatorcontrib>Wolfgang, Christopher L</creatorcontrib><creatorcontrib>Jaffee, Elizabeth M</creatorcontrib><creatorcontrib>Anders, Robert A</creatorcontrib><creatorcontrib>De Jesus-Acosta, Ana</creatorcontrib><creatorcontrib>Zheng, Lei</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>HPB (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bever, Katherine M</au><au>Sugar, Elizabeth A</au><au>Bigelow, Elaine</au><au>Sharma, Rajni</au><au>Laheru, Daniel</au><au>Wolfgang, Christopher L</au><au>Jaffee, Elizabeth M</au><au>Anders, Robert A</au><au>De Jesus-Acosta, Ana</au><au>Zheng, Lei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy</atitle><jtitle>HPB (Oxford, England)</jtitle><addtitle>HPB (Oxford)</addtitle><date>2015-04</date><risdate>2015</risdate><volume>17</volume><issue>4</issue><spage>292</spage><epage>298</epage><pages>292-298</pages><issn>1365-182X</issn><eissn>1477-2574</eissn><abstract>Abstract Background Pancreatic ductal adenocarcinoma (PDA) is comprised of a prominent desmoplastic stromal compartment and only 10–40% of the tumour consists of PDA cells. However, how stromal components should be assessed and how the characteristics of the stromal compartment determine clinical outcomes in PDA patients remain unknown. Method A cohort of 66 consecutive patients who underwent pancreaticoduodenectomy and were primarily followed at Johns Hopkins Hospital between 1998 and 2004, and treated with adjuvant therapy, were included in a retrospective analysis. Resected PDA blocks with good tissue preservation were available for all patients. A new, computer-aided, quantitative method was developed to assess the density and activity of stroma in PDAs and the associations of these characteristics with clinical outcomes. Results High stromal density in resected PDA was found to be significantly associated with longer disease-free [adjusted hazard ratio (aHR) 0.39; P = 0.001] and overall (aHR 0.44; P = 0.004) survival after adjusting for the use of pancreatic cancer vaccine therapy, as well as gender and resection margin positivity. Stromal activity, representing activated pancreatic stellate cells in PDAs, was not significantly associated with the prognosis of resected PDAs. Conclusions These results illustrate the complexity of the role of stroma in PDAs. Further exploration of the prognostic ability of the characteristics of stroma is warranted.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>25250696</pmid><doi>10.1111/hpb.12334</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins - analysis Adult Aged Aged, 80 and over Baltimore Biomarkers, Tumor - analysis Carcinoma, Pancreatic Ductal - chemistry Carcinoma, Pancreatic Ductal - mortality Carcinoma, Pancreatic Ductal - pathology Carcinoma, Pancreatic Ductal - therapy Chemoradiotherapy, Adjuvant Clinical outcomes Collagen - analysis Disease-Free Survival Female Gastroenterology and Hepatology Humans Image Interpretation, Computer-Assisted Immunohistochemistry Kaplan-Meier Estimate Keratins - analysis Male Medical prognosis Medical research Middle Aged Neoplasm, Residual Original Pancreatic cancer Pancreatic Neoplasms - chemistry Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Pancreatic Neoplasms - therapy Pancreaticoduodenectomy Predictive Value of Tests Proportional Hazards Models Retrospective Studies Risk Factors Stromal Cells - chemistry Stromal Cells - pathology Time Factors Treatment Outcome |
| title | The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy |
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