title: Epidermal growth factor receptor status in anaplastic thyroid carcinoma.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) has been reported to be overexpressed in anaplastic thyroid carcinoma (ATC). In vitro studies have shown that EGFR tyrosine kinase inhibitors (TKIs) greatly inhibit cellular growth and induced apoptosis in the ATC cell lines, while somatic mutations in the tyrosine kinase domain or an increased gene copy number are associated with increased sensitivity to TKIs in non-small cell lung cancer.
  
  
  OBJECTIVE
  To investigate the prevalence of EGFR overexpression, gene amplification and activating mutation in the tyrosine kinase domain in patients with ATC.
  
  
  METHODS
  The EGFR gene status and protein expression were investigated by direct DNA sequencing of the hot-spot regions in exons 18, 19 and 21, fluorescence in situ hybridisation (FISH), and immunohistochemistry in tumour tissues from 23 patients with ATC.
  
  
  RESULTS
  On mutational analysis and FISH, neither mutations in the hot-spots nor gene amplification was observed. However, high polysomy was identified in 14/23 (60.9%) patients with ATC. All cases with immunohistochemistry (IHC) positivity (n = 6) had high polysomy, whereas 8/17 (47.1%) cases with IHC negativity had high polysomy (p = 0.048). High polysomy was observed in all 10 cases with giant cell subtype, but in only 4/11 (36.3%) with squamoid and 0/2 with spindle cell sarcomatoid subtype. There was no statistically significant correlation between FISH positivity of ATC tumour and presence of well-differentiated component.
  
  
  CONCLUSIONS
  Despite the low incidence of somatic EGFR gene mutation and amplification in the study samples, in view of the fact that high polysomy was often identified by FISH, as well as the current lack of therapeutic options, EGFR TKIs are worth investigating for treating the patients with ATC who have at least giant cell subtype.
authors.affiliation: Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kong
authors.forename: Myoung Chul
authors.initials: MC
authors.lastname: Kook
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Yang
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Seong Hoe
authors.initials: SH
authors.lastname: Park
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
authors.forename: Bo Youn
authors.initials: BY
authors.lastname: Cho
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Ki-Wook
authors.initials: KW
authors.lastname: Chung
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018773:Genes, erbB-1 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases