title: Anaplastic thyroid carcinoma: expression profile of targets for therapy offers new insights for disease treatment.
abstract: BACKGROUND
  Anaplastic thyroid cancer is an endocrine malignancy. Its rare and rapidly lethal disease course has made it challenging to study. Little is known regarding the expression by anaplastic tumors of molecular targets for new human anticancer agents that have been studied in the preclinical or clinical setting. The objective of this work was to evaluate the expression profile of anaplastic thyroid tumors for molecular targets for treatment.
  
  
  METHODS
  Of the 94 cases of anaplastic thyroid cancers diagnosed and treated in British Columbia, Canada over a 20-year period (1984-2004), 32 cases (34%) had adequate archival tissue available for evaluation. A tissue microarray was constructed from these anaplastic thyroid tumors and immunohistochemistry was utilized to evaluate expression of 31 molecular markers. The markers evaluated were: epidermal growth factor receptor (EGFR), HER2, HER3, HER4, ER, PR, uPA-R, clusterin, E-cadherin, beta-catenin, AMF-R, c-kit, VEGF, ILK, aurora A, aurora B, aurora C, RET, CA-IX, IGF1-R, p53, MDM2, p21, Bcl-2, cyclin D1, cyclin E, p27, calcitonin, MIB-1, TTF-1, and thyroglobulin.
  
  
  RESULTS
  A single tumor with strong calcitonin expression was identified as a poorly differentiated medullary carcinoma and excluded from the study cohort. The mean age of the anaplastic cohort was 66 years; 16 patients (51%) were females, and the median patient survival was 23 weeks. A wide range in molecular marker expression was observed by the anaplastic thyroid cancer tumors (0-100%). The therapeutic targets most frequently and most strongly overexpressed by the anaplastic tumors were: beta-catenin (41%), aurora A (41%), cyclin E (67%), cyclin D1 (77%), and EGFR (84%).
  
  
  CONCLUSIONS
  Anaplastic thyroid tumors exhibit considerable derangement of their cell cycle and multiple signal transduction pathways that leads to uncontrolled cellular proliferation and the development of genomic instability. This report is the first to comprehensively evaluate a panel of molecular targets for therapy of anaplastic thyroid cancer and supports the development of clinical trials with agents such as cetuximab, small-molecule tyrosine kinase inhibitors, and aurora kinase inhibitors, which may offer new hope for individuals diagnosed with this fatal thyroid malignancy.
authors.affiliation: Department of Surgery, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada. smwiseman@providencehealth.bc.ca
authors.forename: Sam M
authors.initials: SM
authors.lastname: Wiseman
authors.forename: Hamid
authors.initials: H
authors.lastname: Masoudi
authors.forename: Paddy
authors.initials: P
authors.lastname: Niblock
authors.forename: Dmitry
authors.initials: D
authors.lastname: Turbin
authors.forename: Ashish
authors.initials: A
authors.lastname: Rajput
authors.forename: John
authors.initials: J
authors.lastname: Hay
authors.forename: Samuel
authors.initials: S
authors.lastname: Bugis
authors.forename: Douglas
authors.initials: D
authors.lastname: Filipenko
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Blake
authors.initials: B
authors.lastname: Gilks
mesh_terms: D000368:Aged; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis; D019927:Cyclin E / Q000096:biosynthesis; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D019927:Cyclin E; D051176:beta Catenin; D019938:Cyclin D1; D066246:ErbB Receptors; C576921:AURKB protein, human; C576927:AURKC protein, human; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases