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Epidermal growth factor receptor status in anaplastic thyroid carcinoma
  1. Dae Ho Lee1,
  2. Geon Kook Lee1,
  3. Sun-young Kong1,
  4. Myoung Chul Kook1,
  5. Sun Kyung Yang1,
  6. So Yeon Park2,
  7. Seong Hoe Park2,
  8. Bhumsuk Keam3,
  9. Do Joon Park3,
  10. Bo Youn Cho3,
  11. Seok Won Kim1,
  12. Ki-Wook Chung1,
  13. Eun Sook Lee1,
  14. Sun Wook Kim1
  1. 1Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea
  2. 2Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
  3. 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  1. Correspondence to:
 Dr Sun Wook Kim
 Research Institute and Hospital, National Cancer Center, Madu-dong 809, Ilsandong-gu, Goyang, Gyeonggi, 410-769, Korea; swkim{at}ncc.re.kr

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.

Aim: 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.

Conclusion: 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.

  • ATC, anaplastic thyroid carcinoma
  • EGFR, epidermal growth factor receptor
  • FISH, fluorescence in situ hybridisation
  • IHC, immunohistochemistry
  • NSCLC, non-small cell lung cancer
  • TKI, tyrosine kinase inhibitor
  • anaplastic thyroid carcinoma
  • EGFR
  • high polysomy

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Footnotes

  • Published Online First 1 November 2006

  • Funding: This work was supported by NCC Grants 610050-1 from the National Cancer Center, Goyang, Gyeonggi, Korea.

  • Competing interests: None declared.

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