Epidermal growth factor receptor overexpression is a marker for adverse pathologic features in papillary thyroid carcinoma

• Type of Material: Article
• Authors: Kevin E. Fisher, Emory University; Jigna C. Jani, Emory University; Sarah B. Fisher, Emory University; Cora Foulks, Emory University; Charles E Hill, Emory University; Collin J Weber, Emory University; Cynthia Cohen, Emory University; Jyotirmay Sharma, Emory University
• Language: English
• Date: 2013-11-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jss.2013.05.003
• Title of Journal or Parent Work: Journal of Surgical Research
• ISSN: 0022-4804
• Volume: 185
• Issue: 1
• Start Page: 217
• End Page: 224
• Grant/Funding Information: SBF is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454.
• Keywords: Life Sciences & Biomedicine; GEFITINIB; Thyroid; EXPRESSION; ACTIVATION; BRAF; EGFR; Carcinoma; Papillary; ASSOCIATION; PHENOTYPE; Science & Technology; CANCER; LUNG ADENOCARCINOMAS; Surgery; Molecular; GENE-MUTATIONS; Immunohistochemistry
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

Background: Epidermal growth factor receptor (EGFR) overexpression (EGFR-H) is implicated in thyroid carcinoma disease progression; however, the clinicopathologic significance of EGFR-H in tumors that harbor EGFR and/or v-Raf murine sarcoma viral oncogene homolog B1 (BRAF)(V600E) mutations is unknown. Methods: Tissue microarrays from 81 patients who had undergone thyroidectomy for carcinoma from 2002-2011 were scored for EGFR expression using immunohistochemistry. Somatic mutations in EGFR exons 19 and 21 and BRAF were analyzed. Correlations between the EGFR immunohistochemistry, EGFR, and BRAF(V600E) mutations and the clinicopathologic features were assessed. Results: EGFR-H was detected in 39.5% of carcinomas (n = 32) from patients with papillary (PTC, 46.2%, n = 18), follicular (29.6%, n = 8), and anaplastic (100.0%, n = 6) but not medullary (0.0%, n = 9) thyroid carcinoma. BRAF(V600E) mutations were identified in 22.2% of the carcinoma cases (n = 18, 15 PTCs and 3 anaplastic thyroid carcinomas). No somatic EGFR mutations were detected in any subtype. On PTC univariate analysis, EGFR-H correlated with increasing stage, extrathyroid extension, tumor capsule invasion, adverse pathologic features (any demonstration of extrathyroid extension, tumor capsule invasion, lymphovascular invasion, lymph node metastasis, and/or distant metastasis), and BRAF(V600E) mutations. On multivariate analysis, EGFR-H correlated with BRAF(V600E) mutations. In BRAF wild-type PTCs, the correlation between EGFR-H and adverse pathologic features approached statistical significance (P = 0.065). Conclusions: EGFR-H could be an important biomarker for aggressive PTCs, particularly in BRAF wild-type PTCs. Despite EGFR-H in PTC, follicular thyroid carcinoma, and anaplastic thyroid carcinoma by immunohistochemistry, somatic EGFR mutations were absent. Therefore, future investigations of EGFR should consider histologic and immunohistochemical methods, in addition to molecular profiling of thyroid carcinomas. This multimodal approach is particularly important for future clinical trials testing anti-EGFR therapy.