{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:57:38Z","timestamp":1790373458962,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,12,10]],"date-time":"2010-12-10T00:00:00Z","timestamp":1291939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chordoma, the molecular hallmark of which is T (brachyury), is a rare malignant bone tumour with a high risk of local recurrence and a tumour from which metastatic disease is a common late event. Currently, there is no effective drug therapy for treating chordomas, although there is evidence that some patients respond to the empirical use of epidermal growth factor receptor (EGFR) antagonists. The aim of this study was to determine the role of EGFR in the pathogenesis of chordoma. Paraffin\u2010embedded material from 173 chordomas from 160 patients [sacro\u2010coccygeal (<jats:italic>n<\/jats:italic> = 94), skull\u2010based (<jats:italic>n<\/jats:italic> = 50), and mobile spine (<jats:italic>n<\/jats:italic> = 16)] was analysed by immunohistochemistry and revealed total EGFR expression in 69% of cases analysed. Of 147 informative chordomas analysed by FISH, 38% revealed high\u2010level EGFR polysomy, 4% high\u2010level polysomy with focal amplification, 18% low\u2010level polysomy, and 39% disomy. Phospho\u2010receptor tyrosine kinase array membranes showed EGFR activation in the chordoma cell line U\u2010CH1 and all of the three chordomas analysed. Direct sequencing of <jats:italic>EGFR<\/jats:italic> (exons 18\u201321), <jats:italic>KRAS, NRAS, HRAS<\/jats:italic> (exons 2, 3), and <jats:italic>BRAF<\/jats:italic> (exons 11, 15) using DNA from 62 chordomas failed to reveal mutations. PTEN expression was absent by immunohistochemistry in 19 of 147 (13%) analysed chordomas, only one of which revealed high\u2010level polysomy of <jats:italic>EGFR<\/jats:italic>. The EGFR inhibitor tyrphostin (AG 1478) markedly inhibited proliferation of the chordoma cell line U\u2010CH1 <jats:italic>in vitro<\/jats:italic> and diminished EGFR phosphorylation in a dose\u2010dependant manner, a finding supported by inhibition of phosphorylated Erk1\/2. p\u2010Akt was suppressed to a much lesser degree in these experiments. There was no reduction of T as assessed by western blotting. These data implicate aberrant EGFR signalling in the pathogenesis of chordoma. This study provides a strategy for patient stratification for treatment with EGFR antagonists. Copyright \u00a9 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2818","type":"journal-article","created":{"date-parts":[[2010,10,29]],"date-time":"2010-10-29T07:33:49Z","timestamp":1288337629000},"page":"336-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["The role of epidermal growth factor receptor in chordoma pathogenesis: a potential therapeutic target"],"prefix":"10.1002","volume":"223","author":[{"given":"Asem","family":"Shalaby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nad\u00e8ge","family":"Presneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Halai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fitim","family":"Berisha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadine","family":"Idowu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Leithner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Liegl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy RW","family":"Briggs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztian","family":"Bacsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars\u2010Gunnar","family":"Kindblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Athanasou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Fernanda","family":"Amary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pancras CW","family":"Hogendoorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Tirabosco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne M","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,12,10]]},"reference":[{"key":"e_1_2_7_3_2","first-page":"315","volume-title":"Pathology and Genetics of Tumours of Soft Tissue and Bone","author":"Mirra JM","year":"2002"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000501)88:9<2122::AID-CNCR19>3.0.CO;2-1"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/72.5.765"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008947301735"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000096283"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/02841860802266672"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e328330c7f0"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji112"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-5-131"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605473"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040938"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2008.059592"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099314"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPST1CTHZS3PSZ"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.06.006"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.4295"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4055"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn541"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1969"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.63"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.3A6195.2004"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-006-0247-9"},{"key":"e_1_2_7_25_2","first-page":"493","article-title":"EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases","volume":"31","author":"Wei Q","year":"2007","journal-title":"Int J Oncol"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605019"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2009.066548"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2097"},{"key":"e_1_2_7_29_2","article-title":"Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional\u2010based study","author":"Presneau N","year":"2010","journal-title":"J Pathol"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.104"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2008.070125"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70130-3"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804385"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990331)81:1<24::AID-IJC5>3.0.CO;2-O"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1086\/321982"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20000701)87:1<68::AID-IJC10>3.0.CO;2-V"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-007-9667-2"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31815b693a"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.01.020"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(01)00547-X"},{"key":"e_1_2_7_41_2","first-page":"595","article-title":"Tyrphostin AG1478 suppresses proliferation and invasion of human breast cancer cells","volume":"33","author":"Zhang YG","year":"2008","journal-title":"Int J Oncol"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004320050290"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-2364"},{"key":"e_1_2_7_44_2","first-page":"1867","article-title":"Combination of PI3K\/mTOR inhibition demonstrates efficacy in human chordoma","volume":"29","author":"Schwab J","year":"2009","journal-title":"Anticancer Res"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2679"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noq003"},{"key":"e_1_2_7_47_2","first-page":"1081","article-title":"[Research of the expression of PTEN in squamous cell carcinoma of larynx by the tissuechip technology]","volume":"21","author":"Wang S","year":"2007","journal-title":"Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65227-3"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1271"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604009"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2009-003"},{"key":"e_1_2_7_52_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.09.111"},{"key":"e_1_2_7_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(05)70102-9"},{"key":"e_1_2_7_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21793"},{"key":"e_1_2_7_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm492"},{"key":"e_1_2_7_56_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.0111"},{"key":"e_1_2_7_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.05.008"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.69.1.79-100.2005"},{"key":"e_1_2_7_59_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.051011"},{"key":"e_1_2_7_60_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-09-0504"},{"key":"e_1_2_7_61_2","first-page":"945","article-title":"Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention","volume":"8","author":"Buettner R","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_62_2","doi-asserted-by":"publisher","DOI":"10.1593\/neo.04571"},{"key":"e_1_2_7_63_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2004.023416"},{"key":"e_1_2_7_64_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-217"},{"key":"e_1_2_7_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602162"},{"key":"e_1_2_7_66_2","doi-asserted-by":"publisher","DOI":"10.3816\/CGC.2007.n.031"},{"key":"e_1_2_7_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.1184"},{"key":"e_1_2_7_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh355"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2818","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:21:08Z","timestamp":1761049268000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,10]]},"references-count":66,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,2]]}},"alternative-id":["10.1002\/path.2818"],"URL":"https:\/\/doi.org\/10.1002\/path.2818","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12,10]]},"assertion":[{"value":"2010-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-10-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-12-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}