High expression and localization of β-catenin and epidermal growth factor receptor identify high risk papillary...

We 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.