{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:23:40Z","timestamp":1790753020372,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,22]],"date-time":"2013-03-22T00:00:00Z","timestamp":1363910400000},"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":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Despite being common in epithelial malignancies, the timing of receptor tyrosine kinase (RTK) up\u2010regulation is poorly understood and therefore hampers the identification of the receptor to target for effective treatment. We aimed to determine if RTK expression changes were early events in carcinogenesis. Oesophageal adenocarcinoma and its pre\u2010invasive lesion, Barrett's oesophagus, were used for immunohistochemical analysis of the RTK panel, EGFR, ErbB2, ErbB3, Met, and FGFR2, by utilizing a cohort of patients with invasive disease (<jats:styled-content>$n = 367$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/path4044_tex2gif-ueqn-1.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content>) and two cohorts with pre\u2010invasive disease, one cross\u2010sectional (<jats:styled-content>$n = 110$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/path4044_tex2gif-ueqn-2.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content>) and one longitudinal in time (<jats:styled-content>$n = 91$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/path4044_tex2gif-ueqn-3.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content>). The results demonstrated that 51% of oesophageal adenocarcinomas overexpressed at least one of the RTK panel, with 21% of these overexpressing multiple receptors. Up\u2010regulation of RTK expression was an early event corresponding with low\u2010grade dysplasia development (25% in areas without dysplasia versus 63% in low\u2010grade dysplasia, <jats:styled-content>$p &lt; 0.001$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/path4044_tex2gif-ueqn-4.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content>). There was a trend for an increase in the prevalence of concomitant overexpression of multiple receptors as intestinal metaplasia progressed to low\u2010grade dysplasia, 7% versus 10%; and from low\u2010grade dysplasia to high\u2010grade dysplasia, 10% versus 19% (<jats:styled-content>$p = 0.06$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/path4044_tex2gif-ueqn-5.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content> and 0.24, respectively). The timing of receptor up\u2010regulation varied; FGFR, ErbB2, and Met overexpression occurred as dysplasia first developed, whilst EGFR overexpression was predominately seen in invasive disease and ErbB3 overexpression was uniformly rare. We provide evidence for a frequent and early role for multiple different RTKs in oesophageal carcinogenesis. Given the early timing of receptor deregulation, inhibiting RTKs in pre\u2010invasive disease may also represent a novel and effective chemopreventive strategy. Copyright \u00a9 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4044","type":"journal-article","created":{"date-parts":[[2012,6,25]],"date-time":"2012-06-25T11:30:10Z","timestamp":1340623810000},"page":"118-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Characterization of the timing and prevalence of receptor tyrosine kinase expression changes in oesophageal carcinogenesis"],"prefix":"10.1002","volume":"230","author":[{"given":"Anna L","family":"Paterson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"O'Donovan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Provenzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam 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