{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T07:57:16Z","timestamp":1776844636882,"version":"3.51.2"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T00:00:00Z","timestamp":1484697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01DL12027"],"award-info":[{"award-number":["01DL12027"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Thymomas and thymic squamous cell carcinomas (<jats:styled-content style=\"fixed-case\">TSQCC<\/jats:styled-content>s) are rare thymic epithelial tumours. Data on angiogenesis and vascular phenotype in these tumours are limited, and no study has taken histological World Health Organization (<jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content>) subtypes into account. The aim of this study was to compare vascularization, pericytes coverage and expression of angiogenic growth factors in different <jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content>\u2010defined subtypes of thymoma<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Vascular density, diameter and architecture and expression of \u03b1\u2010smooth muscle actin (<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>), platelet\u2010derived growth factor (<jats:styled-content style=\"fixed-case\">PDGF<\/jats:styled-content>) receptor\u2010\u03b2 (<jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2), vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>) receptor 1 (<jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>1) and <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> receptor 2 (<jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>2) were investigated in <jats:styled-content style=\"fixed-case\">WHO<\/jats:styled-content> type A, <jats:styled-content style=\"fixed-case\">AB<\/jats:styled-content>, B1, B2 and B3 thymomas and <jats:styled-content style=\"fixed-case\">TSQCC<\/jats:styled-content>s, by the use of immunostaining, quantitative morphometry, and tumour vessel isolation by trypsin digestion. Expression levels of angiopoietin 1 (Ang\u20101), angiopoietin 2 (Ang\u20102), <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010A, <jats:styled-content style=\"fixed-case\">PDGF<\/jats:styled-content>\u2010B and Hif\u20101\u03b1 were examined by quantitative reverse transcription polymerase chain reaction. A and <jats:styled-content style=\"fixed-case\">AB<\/jats:styled-content> thymomas were characterized by a dense network of capillary\u2010like vessels with tight pericyte coverage, whereas B thymomas showed a loose vascular network with increasing vascular diameters and increasing expression of <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PDGFR<\/jats:styled-content>\u03b2 from B1 to B3 thymomas and <jats:styled-content style=\"fixed-case\">TSQCC<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>2 were expressed in vessels of all analysed tumour entities, and at higher levels in epithelial cells of A and B3 thymomas and <jats:styled-content style=\"fixed-case\">TSQCC<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> of Ang\u20102, but not of Ang\u20101, was significantly up\u2010regulated in all thymoma subtypes, with the highest levels being found in A thymomas. In <jats:styled-content style=\"fixed-case\">TSQCC<\/jats:styled-content>s, Ang\u20101 and <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> were the predominantly up\u2010regulated growth factors. Hif\u20101\u03b1 was only up\u2010regulated in B3 thymomas and <jats:styled-content style=\"fixed-case\">TSQCC<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Thymomas and <jats:styled-content style=\"fixed-case\">TSQCC<\/jats:styled-content>s differ significantly in their vascular architecture and expression of key angiogenic growth factors. The findings could help to improve the differential diagnosis of difficult\u2010to\u2010classify thymic epithelial tumours, and indicate different mechanisms of tumour angiogenesis and functional differences of tumour vessels of major thymoma subtypes and <jats:styled-content style=\"fixed-case\">TSQCC<\/jats:styled-content>s.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13114","type":"journal-article","created":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T07:07:11Z","timestamp":1484723231000},"page":"693-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Vascular architecture as a diagnostic marker for differentiation of World Health Organization thymoma subtypes and thymic carcinoma"],"prefix":"10.1111","volume":"70","author":[{"given":"Frederick","family":"Pfister","sequence":"first","affiliation":[{"name":"Department of Nephropathology Institute of Pathology Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg Erlangen Germany"},{"name":"Institute of Pathology University Medical Centre Mannheim University of Heidelberg Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hussam","family":"Hussain","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Centre Mannheim University of Heidelberg Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Djeda","family":"Belharazem","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Centre Mannheim University of Heidelberg Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svenja","family":"Busch","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Centre Mannheim University of Heidelberg Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Simon\u2010Keller","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Centre Mannheim University of Heidelberg Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic","family":"Becker","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Centre Mannheim University of Heidelberg Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Pfister","sequence":"additional","affiliation":[{"name":"Department of Nephropathology Institute of Pathology Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg Erlangen Germany"},{"name":"Institute of Pathology University Medical Centre Mannheim University of Heidelberg Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Rieker","sequence":"additional","affiliation":[{"name":"Institute of Pathology Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Str\u00f6bel","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medicine G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Marx","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Centre Mannheim University of Heidelberg Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000393"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2014.09.124"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000154"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3016"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00316"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0594"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31824fff50"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.49"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12512"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2013.12.003"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603176"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.12056"},{"key":"e_1_2_8_14_1","first-page":"627","article-title":"Angiogenesis in the human thymoma assessed by subclassification of tumor\u2010associated blood vessels and endothelial cells proliferation","volume":"51","author":"Raica M","year":"2010","journal-title":"Rom. J. Morphol. Embryol."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1067\/mtc.2002.124389"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600936290"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200302047"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2639"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s005950170021"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2007.05.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2613.2011.00777.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/978-1-62703-068-7_19","article-title":"Retinal digest preparation: a method to study diabetic retinopathy","volume":"933","author":"Dietrich N","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000663"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81813-9"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/74725"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.55"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1351"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71181-7"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.113.1.147"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64920-6"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-003-0745-x"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.13114","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.13114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T15:11:38Z","timestamp":1696345898000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.13114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,18]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,4]]}},"alternative-id":["10.1111\/his.13114"],"URL":"https:\/\/doi.org\/10.1111\/his.13114","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,18]]},"assertion":[{"value":"2016-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}