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Sam M. Wiseman, MD, FRCSC; Obi L. Griffith, BSc; Shaun Deen, MD; Ashish Rajput, MD; Hamid Masoudi, MD; Blake Gilks, MD, FRCPC; Lynn Goldstein, MD; Allen Gown, MD; Steven J. M. Jones, PhD

Arch Surg. 2007;142:717-729.

Hypothesis  A change in tumor expression profile will be observed during the transformation of differentiated into anaplastic thyroid carcinoma.

Design  Cohort study.

Setting  Population-based sample (British Columbia).

Patients  Sequential archival cases of anaplastic thyroid cancer with an adjacent associated differentiated thyroid cancer focus, and with available paraffin blocks, that had been diagnosed and treated in British Columbia during a 20-year period (12 cases; January 1, 1984, through December 31, 2004) were identified through the provincial tumor registry for tissue microarray construction.

Main Outcome Measure  Significant associations between marker staining and tumor pathologic diagnosis (differentiated vs anaplastic) were determined with contingency table and marginal homogeneity tests. A classifier algorithm was also used to identify useful and important molecular classifiers.

Results  Overall, there were 3 up-regulated and 5 down-regulated markers when comparing the anaplastic carcinoma with associated differentiated thyroid cancers. Contingency table statistics identified 5 markers (thyroglobulin, Bcl-2, MIB-1, E-cadherin, and p53) to be significantly differentially expressed by the anaplastic and differentiated tumor foci. These 5 markers and 3 others (β-catenin, topoisomerase II-, and vascular endothelial growth factor) were significant when evaluated using the marginal homogeneity test. Clustering and classification analysis based on these same 8 markers readily separated differentiated and anaplastic thyroid tumors with a high degree of accuracy.

Conclusion  The markers we observed to change during thyroid tumor progression may not only show promise as molecular diagnostic or prognostic tools but also warrant further study as potential targets for treatment of disease.

Author Affiliations: Department of Surgery, St Paul's Hospital and University of British Columbia (Drs Wiseman, Deen, and Masoudi), Department of Medical Genetics, University of British Columbia, British Columbia Cancer Agency, and Michael Smith Genome Sciences Center (Mr Griffith and Dr Jones), Genetic Pathology Evaluation Center at the Prostate Research Center of Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia (Drs Wiseman, Rajput, and Gilks), and Department of Pathology, University of British Columbia (Drs Gilks and Gown), Vancouver, British Columbia, Canada; and PhenoPath Laboratories, Seattle, Washington (Drs Goldstein and Gown).