title: Epidermal growth factor receptor overexpression is a marker for adverse pathologic features in papillary thyroid carcinoma.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia. Electronic address: kfishe8@emory.edu.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Fisher
authors.forename: Jigna C
authors.initials: JC
authors.lastname: Jani
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Fisher
authors.forename: Cora
authors.initials: C
authors.lastname: Foulks
authors.forename: Charles E
authors.initials: CE
authors.lastname: Hill
authors.forename: Collin J
authors.initials: CJ
authors.lastname: Weber
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.forename: Jyotirmay
authors.initials: J
authors.lastname: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Carcinoma; EGFR; Immunohistochemistry; Molecular; Papillary; Thyroid