Podoplanin expression in cancer‐associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma
Aims Podoplanin expression in cancer‐associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early‐stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expressio...
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| Veröffentlicht in: | Histopathology 2018-02, Vol.72 (3), p.490-499 |
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| creator | Kubouchi, Yasuaki Yurugi, Yohei Wakahara, Makoto Sakabe, Tomohiko Haruki, Tomohiro Nosaka, Kanae Miwa, Ken Araki, Kunio Taniguchi, Yuji Shiomi, Tatsushi Nakamura, Hiroshige Umekita, Yoshihisa |
| description | Aims
Podoplanin expression in cancer‐associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early‐stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p‐stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour–node–metastasis classification for lung cancer.
Methods and results
Immunohistochemical analyses using anti‐podoplanin antibody were performed on resected specimens from 158 patients with p‐stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin‐positive. Podoplanin‐positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin‐positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high‐grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log‐rank test showed that podoplanin‐positive status in CAFs was associated significantly with shorter disease‐free survival (DFS) (P < 0.001) and disease‐specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin‐positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high‐grade components (HR = 3.581, P = 0.013).
Conclusions
Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p‐stage IA lung adenocarcinoma. |
| doi_str_mv | 10.1111/his.13390 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1937527160</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1937527160</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4720-e96a5d1e6a656724d6a304b592ad4516a57d4d85db95f908d94b6a88df2513a73</originalsourceid><addsrcrecordid>eNp1kc1qFTEUx4Mo9ra68AVkwI1dTJuPydeyFG0vFCyo6-FMkrk3JTe5JjOt3fkIQt_QJzHXW10IzSY5yY8f5-SP0BuCT0hdp2tfTghjGj9DC8IEbynn-jlaYIZ1i4mQB-iwlBuMiWSUvkQHVClFcCcX6OE62bQNEH1s3PdtdqX4FJtaGYjG5V8_fkIpyXiYnG1GP-Q0BChTaSprvamHOY5wm-YMQ3D1Nq1iKr7sFFuYvIsVufPTeletU0grbyA0ZYKVa5ZnTZjjqgHrYjKQjY9pA6_QixFCca8f9yP09eOHL-eX7dWni-X52VVrOklx67QAbokTILiQtLMCGO4GrinYjpP6KG1nFbeD5qPGyupuEKCUHSknDCQ7Qu_33tr0t9mVqd_4Ylyov-HSXHqimeRUEoEr-u4_9KZOHGt3lVIK445hVqnjPWVyKiW7sd9mv4F83xPc75Lqa1L9n6Qq-_bROA8bZ_-Rf6OpwOkeuPPB3T9t6i-Xn_fK36BboQg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1988004303</pqid></control><display><type>article</type><title>Podoplanin expression in cancer‐associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><creator>Kubouchi, Yasuaki ; Yurugi, Yohei ; Wakahara, Makoto ; Sakabe, Tomohiko ; Haruki, Tomohiro ; Nosaka, Kanae ; Miwa, Ken ; Araki, Kunio ; Taniguchi, Yuji ; Shiomi, Tatsushi ; Nakamura, Hiroshige ; Umekita, Yoshihisa</creator><creatorcontrib>Kubouchi, Yasuaki ; Yurugi, Yohei ; Wakahara, Makoto ; Sakabe, Tomohiko ; Haruki, Tomohiro ; Nosaka, Kanae ; Miwa, Ken ; Araki, Kunio ; Taniguchi, Yuji ; Shiomi, Tatsushi ; Nakamura, Hiroshige ; Umekita, Yoshihisa</creatorcontrib><description>Aims
Podoplanin expression in cancer‐associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early‐stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p‐stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour–node–metastasis classification for lung cancer.
Methods and results
Immunohistochemical analyses using anti‐podoplanin antibody were performed on resected specimens from 158 patients with p‐stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin‐positive. Podoplanin‐positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin‐positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high‐grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log‐rank test showed that podoplanin‐positive status in CAFs was associated significantly with shorter disease‐free survival (DFS) (P < 0.001) and disease‐specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin‐positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high‐grade components (HR = 3.581, P = 0.013).
Conclusions
Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p‐stage IA lung adenocarcinoma.</description><identifier>ISSN: 0309-0167</identifier><identifier>EISSN: 1365-2559</identifier><identifier>DOI: 10.1111/his.13390</identifier><identifier>PMID: 28881047</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adenocarcinoma ; Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Adenocarcinoma of Lung ; Aged ; Biomarkers, Tumor - analysis ; Cancer ; Cancer-Associated Fibroblasts - pathology ; cancer‐associated fibroblast ; Disease-Free Survival ; Female ; Fibroblasts ; Humans ; Immunoreactivity ; Kaplan-Meier Estimate ; Lung cancer ; Lung carcinoma ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Male ; Medical prognosis ; Membrane Glycoproteins - analysis ; Membrane Glycoproteins - biosynthesis ; Metastases ; Middle Aged ; Multivariate analysis ; Neoplasm Recurrence, Local - pathology ; podoplain ; Prognosis ; Squamous cell carcinoma ; Tumors</subject><ispartof>Histopathology, 2018-02, Vol.72 (3), p.490-499</ispartof><rights>2017 John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons Ltd.</rights><rights>Copyright © 2018 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4720-e96a5d1e6a656724d6a304b592ad4516a57d4d85db95f908d94b6a88df2513a73</citedby><cites>FETCH-LOGICAL-c4720-e96a5d1e6a656724d6a304b592ad4516a57d4d85db95f908d94b6a88df2513a73</cites><orcidid>0000-0002-2846-390X ; 0000-0002-7734-2354</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhis.13390$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhis.13390$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28881047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kubouchi, Yasuaki</creatorcontrib><creatorcontrib>Yurugi, Yohei</creatorcontrib><creatorcontrib>Wakahara, Makoto</creatorcontrib><creatorcontrib>Sakabe, Tomohiko</creatorcontrib><creatorcontrib>Haruki, Tomohiro</creatorcontrib><creatorcontrib>Nosaka, Kanae</creatorcontrib><creatorcontrib>Miwa, Ken</creatorcontrib><creatorcontrib>Araki, Kunio</creatorcontrib><creatorcontrib>Taniguchi, Yuji</creatorcontrib><creatorcontrib>Shiomi, Tatsushi</creatorcontrib><creatorcontrib>Nakamura, Hiroshige</creatorcontrib><creatorcontrib>Umekita, Yoshihisa</creatorcontrib><title>Podoplanin expression in cancer‐associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma</title><title>Histopathology</title><addtitle>Histopathology</addtitle><description>Aims
Podoplanin expression in cancer‐associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early‐stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p‐stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour–node–metastasis classification for lung cancer.
Methods and results
Immunohistochemical analyses using anti‐podoplanin antibody were performed on resected specimens from 158 patients with p‐stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin‐positive. Podoplanin‐positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin‐positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high‐grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log‐rank test showed that podoplanin‐positive status in CAFs was associated significantly with shorter disease‐free survival (DFS) (P < 0.001) and disease‐specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin‐positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high‐grade components (HR = 3.581, P = 0.013).
Conclusions
Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p‐stage IA lung adenocarcinoma.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma of Lung</subject><subject>Aged</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Cancer</subject><subject>Cancer-Associated Fibroblasts - pathology</subject><subject>cancer‐associated fibroblast</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Humans</subject><subject>Immunoreactivity</subject><subject>Kaplan-Meier Estimate</subject><subject>Lung cancer</subject><subject>Lung carcinoma</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Membrane Glycoproteins - analysis</subject><subject>Membrane Glycoproteins - biosynthesis</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>podoplain</subject><subject>Prognosis</subject><subject>Squamous cell carcinoma</subject><subject>Tumors</subject><issn>0309-0167</issn><issn>1365-2559</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1qFTEUx4Mo9ra68AVkwI1dTJuPydeyFG0vFCyo6-FMkrk3JTe5JjOt3fkIQt_QJzHXW10IzSY5yY8f5-SP0BuCT0hdp2tfTghjGj9DC8IEbynn-jlaYIZ1i4mQB-iwlBuMiWSUvkQHVClFcCcX6OE62bQNEH1s3PdtdqX4FJtaGYjG5V8_fkIpyXiYnG1GP-Q0BChTaSprvamHOY5wm-YMQ3D1Nq1iKr7sFFuYvIsVufPTeletU0grbyA0ZYKVa5ZnTZjjqgHrYjKQjY9pA6_QixFCca8f9yP09eOHL-eX7dWni-X52VVrOklx67QAbokTILiQtLMCGO4GrinYjpP6KG1nFbeD5qPGyupuEKCUHSknDCQ7Qu_33tr0t9mVqd_4Ylyov-HSXHqimeRUEoEr-u4_9KZOHGt3lVIK445hVqnjPWVyKiW7sd9mv4F83xPc75Lqa1L9n6Qq-_bROA8bZ_-Rf6OpwOkeuPPB3T9t6i-Xn_fK36BboQg</recordid><startdate>201802</startdate><enddate>201802</enddate><creator>Kubouchi, Yasuaki</creator><creator>Yurugi, Yohei</creator><creator>Wakahara, Makoto</creator><creator>Sakabe, Tomohiko</creator><creator>Haruki, Tomohiro</creator><creator>Nosaka, Kanae</creator><creator>Miwa, Ken</creator><creator>Araki, Kunio</creator><creator>Taniguchi, Yuji</creator><creator>Shiomi, Tatsushi</creator><creator>Nakamura, Hiroshige</creator><creator>Umekita, Yoshihisa</creator><general>Wiley Subscription Services, 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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2846-390X</orcidid><orcidid>https://orcid.org/0000-0002-7734-2354</orcidid></search><sort><creationdate>201802</creationdate><title>Podoplanin expression in cancer‐associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma</title><author>Kubouchi, Yasuaki ; Yurugi, Yohei ; Wakahara, Makoto ; Sakabe, Tomohiko ; Haruki, Tomohiro ; Nosaka, Kanae ; Miwa, Ken ; Araki, Kunio ; Taniguchi, Yuji ; Shiomi, Tatsushi ; Nakamura, Hiroshige ; Umekita, Yoshihisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4720-e96a5d1e6a656724d6a304b592ad4516a57d4d85db95f908d94b6a88df2513a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma of Lung</topic><topic>Aged</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Cancer</topic><topic>Cancer-Associated Fibroblasts - pathology</topic><topic>cancer‐associated fibroblast</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Humans</topic><topic>Immunoreactivity</topic><topic>Kaplan-Meier Estimate</topic><topic>Lung cancer</topic><topic>Lung carcinoma</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Membrane Glycoproteins - analysis</topic><topic>Membrane Glycoproteins - biosynthesis</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>podoplain</topic><topic>Prognosis</topic><topic>Squamous cell carcinoma</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kubouchi, Yasuaki</creatorcontrib><creatorcontrib>Yurugi, Yohei</creatorcontrib><creatorcontrib>Wakahara, Makoto</creatorcontrib><creatorcontrib>Sakabe, Tomohiko</creatorcontrib><creatorcontrib>Haruki, Tomohiro</creatorcontrib><creatorcontrib>Nosaka, Kanae</creatorcontrib><creatorcontrib>Miwa, Ken</creatorcontrib><creatorcontrib>Araki, Kunio</creatorcontrib><creatorcontrib>Taniguchi, Yuji</creatorcontrib><creatorcontrib>Shiomi, Tatsushi</creatorcontrib><creatorcontrib>Nakamura, Hiroshige</creatorcontrib><creatorcontrib>Umekita, Yoshihisa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Histopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kubouchi, Yasuaki</au><au>Yurugi, Yohei</au><au>Wakahara, Makoto</au><au>Sakabe, Tomohiko</au><au>Haruki, Tomohiro</au><au>Nosaka, Kanae</au><au>Miwa, Ken</au><au>Araki, Kunio</au><au>Taniguchi, Yuji</au><au>Shiomi, Tatsushi</au><au>Nakamura, Hiroshige</au><au>Umekita, Yoshihisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Podoplanin expression in cancer‐associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma</atitle><jtitle>Histopathology</jtitle><addtitle>Histopathology</addtitle><date>2018-02</date><risdate>2018</risdate><volume>72</volume><issue>3</issue><spage>490</spage><epage>499</epage><pages>490-499</pages><issn>0309-0167</issn><eissn>1365-2559</eissn><abstract>Aims
Podoplanin expression in cancer‐associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early‐stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p‐stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour–node–metastasis classification for lung cancer.
Methods and results
Immunohistochemical analyses using anti‐podoplanin antibody were performed on resected specimens from 158 patients with p‐stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin‐positive. Podoplanin‐positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin‐positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high‐grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log‐rank test showed that podoplanin‐positive status in CAFs was associated significantly with shorter disease‐free survival (DFS) (P < 0.001) and disease‐specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin‐positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high‐grade components (HR = 3.581, P = 0.013).
Conclusions
Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p‐stage IA lung adenocarcinoma.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28881047</pmid><doi>10.1111/his.13390</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-2846-390X</orcidid><orcidid>https://orcid.org/0000-0002-7734-2354</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Adenocarcinoma - mortality Adenocarcinoma - pathology Adenocarcinoma of Lung Aged Biomarkers, Tumor - analysis Cancer Cancer-Associated Fibroblasts - pathology cancer‐associated fibroblast Disease-Free Survival Female Fibroblasts Humans Immunoreactivity Kaplan-Meier Estimate Lung cancer Lung carcinoma Lung Neoplasms - mortality Lung Neoplasms - pathology Male Medical prognosis Membrane Glycoproteins - analysis Membrane Glycoproteins - biosynthesis Metastases Middle Aged Multivariate analysis Neoplasm Recurrence, Local - pathology podoplain Prognosis Squamous cell carcinoma Tumors |
| title | Podoplanin expression in cancer‐associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma |
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