Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile
Aims Infiltrating epitheliosis is a rare complex sclerosing lesion (CSL) of the breast, characterized by infiltrating ducts immersed in a scleroelastotic stroma and filled with cells having architectural and cytological patterns reminiscent of those of usual ductal hyperplasia. In this study we soug...
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| Veröffentlicht in: | Histopathology 2016-06, Vol.68 (7), p.1030-1039 |
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| container_title | Histopathology |
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| creator | Eberle, Carey A Piscuoglio, Salvatore Rakha, Emad A Ng, Charlotte K Y Geyer, Felipe C Edelweiss, Marcia Sakr, Rita A Weigelt, Britta Reis-Filho, Jorge S Ellis, Ian O |
| description | Aims
Infiltrating epitheliosis is a rare complex sclerosing lesion (CSL) of the breast, characterized by infiltrating ducts immersed in a scleroelastotic stroma and filled with cells having architectural and cytological patterns reminiscent of those of usual ductal hyperplasia. In this study we sought to define the molecular characteristics of infiltrating epitheliosis.
Methods and results
Eight infiltrating epitheliosis, adjacent breast lesions (one usual ductal hyperplasia, one papilloma, one micropapillary ductal carcinoma in situ and one low‐grade adenosquamous carcinoma), and corresponding normal breast tissue from each case were microdissected and subjected to massively parallel sequencing analysis targeting all coding regions of 254 genes mutated recurrently in breast cancer and/or related to DNA repair. Mutations in components of the PI3K pathway were found in all infiltrating epitheliosis samples, seven of which harboured PIK3CA hotspot mutations, while the remaining case displayed a PIK3R1 somatic mutation.
Conclusions
Somatic mutations affecting PI3K pathway genes were found to be highly prevalent in infiltrating epitheliosis, suggesting that these lesions may be neoplastic rather than hyperplastic. The landscape of somatic genetic alterations found in infiltrating epitheliosis is similar to that of radial scars/CSLs, suggesting that infiltrating epitheliosis may represent one end of this spectrum of lesions. |
| doi_str_mv | 10.1111/his.12897 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1787472153</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1787472153</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4267-9551742c0429d44c7ed8dcbbd0641e72ef9241430330e2ecf54b24829d0caa2f3</originalsourceid><addsrcrecordid>eNp1kV9LHDEUxYNYdKt96BeQgC8tdDR_Jzu-FanuglSwLUJfQiZzZzc6M5kmGez20ze66kOh9-Vyye-eE85F6D0lJzTX6drFE8rmldpBM8pLWTApq100I5xUBaGl2kdvY7wjhCrO2B7aZ6WoFGVshh6WQ-u6FExywwrD6NIaOueji9i3OA-4DmBiOsN2bYKxCYL7k2E_PL5n4-Q7v3LWdLgFk6YA8RN2fT8NflzD4NNmBGyGBq_y0DuLx-CzIRyiN63pIrx77gfox8WX7-eL4ur6cnn--aqwgpWqqKSkSjBLBKsaIayCZt7Yum5IKSgoBm3FBBWccE6AgW2lqJmYZ5hYY1jLD9CHrW72_TVBTLp30ULXmQH8FDVVcyUUo5Jn9Pgf9M5PYci_e6IIL7mkmfq4pWzwMQZo9Rhcb8JGU6Ifr6FzKPrpGpk9elac6h6aV_Il_gycboGHHMnm_0p6sfz2IllsN3Ly8Pt1w4R7XSqupL79eql_Xtws2K2s9A3_Cz_5pKU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1787036351</pqid></control><display><type>article</type><title>Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Eberle, Carey A ; Piscuoglio, Salvatore ; Rakha, Emad A ; Ng, Charlotte K Y ; Geyer, Felipe C ; Edelweiss, Marcia ; Sakr, Rita A ; Weigelt, Britta ; Reis-Filho, Jorge S ; Ellis, Ian O</creator><creatorcontrib>Eberle, Carey A ; Piscuoglio, Salvatore ; Rakha, Emad A ; Ng, Charlotte K Y ; Geyer, Felipe C ; Edelweiss, Marcia ; Sakr, Rita A ; Weigelt, Britta ; Reis-Filho, Jorge S ; Ellis, Ian O</creatorcontrib><description>Aims
Infiltrating epitheliosis is a rare complex sclerosing lesion (CSL) of the breast, characterized by infiltrating ducts immersed in a scleroelastotic stroma and filled with cells having architectural and cytological patterns reminiscent of those of usual ductal hyperplasia. In this study we sought to define the molecular characteristics of infiltrating epitheliosis.
Methods and results
Eight infiltrating epitheliosis, adjacent breast lesions (one usual ductal hyperplasia, one papilloma, one micropapillary ductal carcinoma in situ and one low‐grade adenosquamous carcinoma), and corresponding normal breast tissue from each case were microdissected and subjected to massively parallel sequencing analysis targeting all coding regions of 254 genes mutated recurrently in breast cancer and/or related to DNA repair. Mutations in components of the PI3K pathway were found in all infiltrating epitheliosis samples, seven of which harboured PIK3CA hotspot mutations, while the remaining case displayed a PIK3R1 somatic mutation.
Conclusions
Somatic mutations affecting PI3K pathway genes were found to be highly prevalent in infiltrating epitheliosis, suggesting that these lesions may be neoplastic rather than hyperplastic. The landscape of somatic genetic alterations found in infiltrating epitheliosis is similar to that of radial scars/CSLs, suggesting that infiltrating epitheliosis may represent one end of this spectrum of lesions.</description><identifier>ISSN: 0309-0167</identifier><identifier>EISSN: 1365-2559</identifier><identifier>DOI: 10.1111/his.12897</identifier><identifier>PMID: 26497122</identifier><identifier>CODEN: HISTDD</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Aged ; Aged, 80 and over ; Breast - metabolism ; Breast - pathology ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Carcinoma, Adenosquamous - genetics ; Carcinoma, Adenosquamous - metabolism ; Carcinoma, Adenosquamous - pathology ; Carcinoma, Intraductal, Noninfiltrating - genetics ; Carcinoma, Intraductal, Noninfiltrating - metabolism ; Carcinoma, Intraductal, Noninfiltrating - pathology ; Class I Phosphatidylinositol 3-Kinases - genetics ; complex sclerosing lesions ; Female ; Fibrocystic Breast Disease - genetics ; Fibrocystic Breast Disease - metabolism ; Fibrocystic Breast Disease - pathology ; High-Throughput Nucleotide Sequencing ; Humans ; Hyperplasia ; immunohistochemistry ; Immunophenotyping ; infiltrating epitheliosis ; Mammography ; massively parallel sequencing ; Middle Aged ; Mutation ; Papilloma - genetics ; Papilloma - metabolism ; Papilloma - pathology ; Sclerosis - genetics ; Sclerosis - metabolism ; Sclerosis - pathology ; Sequence Analysis, DNA</subject><ispartof>Histopathology, 2016-06, Vol.68 (7), p.1030-1039</ispartof><rights>2015 John Wiley & Sons Ltd</rights><rights>2015 John Wiley & Sons Ltd.</rights><rights>Copyright © 2016 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4267-9551742c0429d44c7ed8dcbbd0641e72ef9241430330e2ecf54b24829d0caa2f3</citedby><cites>FETCH-LOGICAL-c4267-9551742c0429d44c7ed8dcbbd0641e72ef9241430330e2ecf54b24829d0caa2f3</cites></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.12897$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhis.12897$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,27931,27932,45581,45582</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26497122$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eberle, Carey A</creatorcontrib><creatorcontrib>Piscuoglio, Salvatore</creatorcontrib><creatorcontrib>Rakha, Emad A</creatorcontrib><creatorcontrib>Ng, Charlotte K Y</creatorcontrib><creatorcontrib>Geyer, Felipe C</creatorcontrib><creatorcontrib>Edelweiss, Marcia</creatorcontrib><creatorcontrib>Sakr, Rita A</creatorcontrib><creatorcontrib>Weigelt, Britta</creatorcontrib><creatorcontrib>Reis-Filho, Jorge S</creatorcontrib><creatorcontrib>Ellis, Ian O</creatorcontrib><title>Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile</title><title>Histopathology</title><addtitle>Histopathology</addtitle><description>Aims
Infiltrating epitheliosis is a rare complex sclerosing lesion (CSL) of the breast, characterized by infiltrating ducts immersed in a scleroelastotic stroma and filled with cells having architectural and cytological patterns reminiscent of those of usual ductal hyperplasia. In this study we sought to define the molecular characteristics of infiltrating epitheliosis.
Methods and results
Eight infiltrating epitheliosis, adjacent breast lesions (one usual ductal hyperplasia, one papilloma, one micropapillary ductal carcinoma in situ and one low‐grade adenosquamous carcinoma), and corresponding normal breast tissue from each case were microdissected and subjected to massively parallel sequencing analysis targeting all coding regions of 254 genes mutated recurrently in breast cancer and/or related to DNA repair. Mutations in components of the PI3K pathway were found in all infiltrating epitheliosis samples, seven of which harboured PIK3CA hotspot mutations, while the remaining case displayed a PIK3R1 somatic mutation.
Conclusions
Somatic mutations affecting PI3K pathway genes were found to be highly prevalent in infiltrating epitheliosis, suggesting that these lesions may be neoplastic rather than hyperplastic. The landscape of somatic genetic alterations found in infiltrating epitheliosis is similar to that of radial scars/CSLs, suggesting that infiltrating epitheliosis may represent one end of this spectrum of lesions.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Breast - metabolism</subject><subject>Breast - pathology</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Carcinoma, Adenosquamous - genetics</subject><subject>Carcinoma, Adenosquamous - metabolism</subject><subject>Carcinoma, Adenosquamous - pathology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - genetics</subject><subject>Carcinoma, Intraductal, Noninfiltrating - metabolism</subject><subject>Carcinoma, Intraductal, Noninfiltrating - pathology</subject><subject>Class I Phosphatidylinositol 3-Kinases - genetics</subject><subject>complex sclerosing lesions</subject><subject>Female</subject><subject>Fibrocystic Breast Disease - genetics</subject><subject>Fibrocystic Breast Disease - metabolism</subject><subject>Fibrocystic Breast Disease - pathology</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Hyperplasia</subject><subject>immunohistochemistry</subject><subject>Immunophenotyping</subject><subject>infiltrating epitheliosis</subject><subject>Mammography</subject><subject>massively parallel sequencing</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Papilloma - genetics</subject><subject>Papilloma - metabolism</subject><subject>Papilloma - pathology</subject><subject>Sclerosis - genetics</subject><subject>Sclerosis - metabolism</subject><subject>Sclerosis - pathology</subject><subject>Sequence Analysis, DNA</subject><issn>0309-0167</issn><issn>1365-2559</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV9LHDEUxYNYdKt96BeQgC8tdDR_Jzu-FanuglSwLUJfQiZzZzc6M5kmGez20ze66kOh9-Vyye-eE85F6D0lJzTX6drFE8rmldpBM8pLWTApq100I5xUBaGl2kdvY7wjhCrO2B7aZ6WoFGVshh6WQ-u6FExywwrD6NIaOueji9i3OA-4DmBiOsN2bYKxCYL7k2E_PL5n4-Q7v3LWdLgFk6YA8RN2fT8NflzD4NNmBGyGBq_y0DuLx-CzIRyiN63pIrx77gfox8WX7-eL4ur6cnn--aqwgpWqqKSkSjBLBKsaIayCZt7Yum5IKSgoBm3FBBWccE6AgW2lqJmYZ5hYY1jLD9CHrW72_TVBTLp30ULXmQH8FDVVcyUUo5Jn9Pgf9M5PYci_e6IIL7mkmfq4pWzwMQZo9Rhcb8JGU6Ifr6FzKPrpGpk9elac6h6aV_Il_gycboGHHMnm_0p6sfz2IllsN3Ly8Pt1w4R7XSqupL79eql_Xtws2K2s9A3_Cz_5pKU</recordid><startdate>201606</startdate><enddate>201606</enddate><creator>Eberle, Carey A</creator><creator>Piscuoglio, Salvatore</creator><creator>Rakha, Emad A</creator><creator>Ng, Charlotte K Y</creator><creator>Geyer, Felipe C</creator><creator>Edelweiss, Marcia</creator><creator>Sakr, Rita A</creator><creator>Weigelt, Britta</creator><creator>Reis-Filho, Jorge S</creator><creator>Ellis, Ian O</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>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></search><sort><creationdate>201606</creationdate><title>Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile</title><author>Eberle, Carey A ; Piscuoglio, Salvatore ; Rakha, Emad A ; Ng, Charlotte K Y ; Geyer, Felipe C ; Edelweiss, Marcia ; Sakr, Rita A ; Weigelt, Britta ; Reis-Filho, Jorge S ; Ellis, Ian O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4267-9551742c0429d44c7ed8dcbbd0641e72ef9241430330e2ecf54b24829d0caa2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Breast - metabolism</topic><topic>Breast - pathology</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Carcinoma, Adenosquamous - genetics</topic><topic>Carcinoma, Adenosquamous - metabolism</topic><topic>Carcinoma, Adenosquamous - pathology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - genetics</topic><topic>Carcinoma, Intraductal, Noninfiltrating - metabolism</topic><topic>Carcinoma, Intraductal, Noninfiltrating - pathology</topic><topic>Class I Phosphatidylinositol 3-Kinases - genetics</topic><topic>complex sclerosing lesions</topic><topic>Female</topic><topic>Fibrocystic Breast Disease - genetics</topic><topic>Fibrocystic Breast Disease - metabolism</topic><topic>Fibrocystic Breast Disease - pathology</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Hyperplasia</topic><topic>immunohistochemistry</topic><topic>Immunophenotyping</topic><topic>infiltrating epitheliosis</topic><topic>Mammography</topic><topic>massively parallel sequencing</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Papilloma - genetics</topic><topic>Papilloma - metabolism</topic><topic>Papilloma - pathology</topic><topic>Sclerosis - genetics</topic><topic>Sclerosis - metabolism</topic><topic>Sclerosis - pathology</topic><topic>Sequence Analysis, DNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eberle, Carey A</creatorcontrib><creatorcontrib>Piscuoglio, Salvatore</creatorcontrib><creatorcontrib>Rakha, Emad A</creatorcontrib><creatorcontrib>Ng, Charlotte K Y</creatorcontrib><creatorcontrib>Geyer, Felipe C</creatorcontrib><creatorcontrib>Edelweiss, Marcia</creatorcontrib><creatorcontrib>Sakr, Rita A</creatorcontrib><creatorcontrib>Weigelt, Britta</creatorcontrib><creatorcontrib>Reis-Filho, Jorge S</creatorcontrib><creatorcontrib>Ellis, Ian O</creatorcontrib><collection>Istex</collection><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>Eberle, Carey A</au><au>Piscuoglio, Salvatore</au><au>Rakha, Emad A</au><au>Ng, Charlotte K Y</au><au>Geyer, Felipe C</au><au>Edelweiss, Marcia</au><au>Sakr, Rita A</au><au>Weigelt, Britta</au><au>Reis-Filho, Jorge S</au><au>Ellis, Ian O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile</atitle><jtitle>Histopathology</jtitle><addtitle>Histopathology</addtitle><date>2016-06</date><risdate>2016</risdate><volume>68</volume><issue>7</issue><spage>1030</spage><epage>1039</epage><pages>1030-1039</pages><issn>0309-0167</issn><eissn>1365-2559</eissn><coden>HISTDD</coden><abstract>Aims
Infiltrating epitheliosis is a rare complex sclerosing lesion (CSL) of the breast, characterized by infiltrating ducts immersed in a scleroelastotic stroma and filled with cells having architectural and cytological patterns reminiscent of those of usual ductal hyperplasia. In this study we sought to define the molecular characteristics of infiltrating epitheliosis.
Methods and results
Eight infiltrating epitheliosis, adjacent breast lesions (one usual ductal hyperplasia, one papilloma, one micropapillary ductal carcinoma in situ and one low‐grade adenosquamous carcinoma), and corresponding normal breast tissue from each case were microdissected and subjected to massively parallel sequencing analysis targeting all coding regions of 254 genes mutated recurrently in breast cancer and/or related to DNA repair. Mutations in components of the PI3K pathway were found in all infiltrating epitheliosis samples, seven of which harboured PIK3CA hotspot mutations, while the remaining case displayed a PIK3R1 somatic mutation.
Conclusions
Somatic mutations affecting PI3K pathway genes were found to be highly prevalent in infiltrating epitheliosis, suggesting that these lesions may be neoplastic rather than hyperplastic. The landscape of somatic genetic alterations found in infiltrating epitheliosis is similar to that of radial scars/CSLs, suggesting that infiltrating epitheliosis may represent one end of this spectrum of lesions.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>26497122</pmid><doi>10.1111/his.12897</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Breast - metabolism Breast - pathology Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Carcinoma, Adenosquamous - genetics Carcinoma, Adenosquamous - metabolism Carcinoma, Adenosquamous - pathology Carcinoma, Intraductal, Noninfiltrating - genetics Carcinoma, Intraductal, Noninfiltrating - metabolism Carcinoma, Intraductal, Noninfiltrating - pathology Class I Phosphatidylinositol 3-Kinases - genetics complex sclerosing lesions Female Fibrocystic Breast Disease - genetics Fibrocystic Breast Disease - metabolism Fibrocystic Breast Disease - pathology High-Throughput Nucleotide Sequencing Humans Hyperplasia immunohistochemistry Immunophenotyping infiltrating epitheliosis Mammography massively parallel sequencing Middle Aged Mutation Papilloma - genetics Papilloma - metabolism Papilloma - pathology Sclerosis - genetics Sclerosis - metabolism Sclerosis - pathology Sequence Analysis, DNA |
| title | Infiltrating epitheliosis of the breast: characterization of histological features, immunophenotype and genomic profile |
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