Išić Denčić, Tijana (13008078500)Tijana (13008078500)Išić DenčićBartolome, Aleksandar (57052636000)Aleksandar (57052636000)BartolomeŠelemetjev, Sonja (24463032600)Sonja (24463032600)ŠelemetjevĐorić, Ilona (57210359065)Ilona (57210359065)ĐorićTatić, Svetislav (6701763955)Svetislav (6701763955)TatićŽivaljević, Vladan (6701787012)Vladan (6701787012)ŽivaljevićCvejić, Dubravka (7003808274)Dubravka (7003808274)Cvejić2025-06-122025-06-122018https://doi.org/10.1016/j.yexmp.2018.08.001https://www.scopus.com/inward/record.uri?eid=2-s2.0-85051115050&doi=10.1016%2fj.yexmp.2018.08.001&partnerID=40&md5=85762cdf10ed3270d064c41ed1d21f06https://remedy.med.bg.ac.rs/handle/123456789/6068We have evaluated the clinical significance of deregulated expression of β-catenin and epidermal growth factor receptor (EGFR) during papillary thyroid carcinoma (PTC) progression. Immunohistochemical expression of β-catenin and EGFR was analyzed in 104 archival tissues of PTC and 19 matched lymph node metastases (LNMs). β-catenin (39/104, 37.5%) and EGFR (58/104, 55.7%) were co-expressed and co-localized in primary PTCs (p <.0001), which was confirmed by double immunofluorescent staining. The high expression of each molecule, as well as their high cytosolic co-expression, correlated with adverse clinicopathological features of the patients (p <.05). High expression of the proteins did not associate with the presence of BRAFV600E mutation (p >.05), tested by mutant allele-specific PCR amplification. Although nuclear localization of β-catenin was found in a subset of PTC patients (16/104, 15.4%), no β-catenin mutations were found in exon 3 of the CTNNB1 gene (screened by PCR in combination with denaturing gradient gel electrophoresis and confirmed by next generation sequencing). Cases with additional nuclear β-catenin staining showed strong association with high EGFR expression (15/16, 93.7%), the presence of capsule invasion (12/16, 81.25%) and regional LNM (9/16, 52.3%). In corresponding LNMs, β-catenin and EGFR expressions were maintained at high levels or further increased. Co-expression of high levels of β-catenin and EGFR in association with clinicopathological features implicates their clinical utility in risk stratification of PTC patients, and supports the possibility of crosstalk between Wnt/β-catenin and EGFR signaling during PTC progression. © 2018 Elsevier Inc.Epidermal growth factor receptorPapillary thyroid carcinomaPredictive biomarkerRisk stratificationβ-CateninHigh expression and localization of β-catenin and epidermal growth factor receptor identify high risk papillary thyroid carcinoma patients