Identification of molecular markers altered during transformation of differentiated into anaplastic thyroid carcinoma.

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 cancerwith an adjacent associated differentiated thyroid cancerfocus, 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 microarrayconstruction. Main Outcome Measure Significant associations between marker staining and tumor pathologic diagnosis (differentiated vs anaplastic) were determined with contingency tableand 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 carcinomawith associated differentiated thyroid cancers. Contingency tablestatistics 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-α, 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 tumorswith a high degree of accuracy. Conclusion The markers we observed to change during thyroid tumorprogression may not only show promise as molecular diagnostic or prognostic tools but also warrant further study as potential targets for treatment of disease.