Immunophenotyping of thyroid tumors identifies molecular markers altered during transformation of differentiated into...

The objective of this study was to evaluate the change in the tumor expression profile that occurs during the transformation of differentiated thyroid cancer (DTC) into anaplastic thyroid cancer (ATC) and to evaluate an 8-marker transformation panel previously identified through evaluation of ATCs and their adjacent associated DTCs.

Tissue microarrays were constructed from 19 ATCs and 96 DTCs (90 papillary carcinomas and 6 follicular carcinomas), and immunohistochemistry was used to evaluate the expression of 54 molecular markers. Significant associations between marker staining and cancer pathology (DTC vs ATC) were determined using contingency table and marginal homogeneity tests. A Random Forests classifier algorithm was also used to identify useful or important molecular classifiers.

Overall, there were 25 significantly differentially expressed markers when comparing ATCs with DTCs. These included 5 of the 8 markers that were previously identified as being altered during anaplastic transformation and 3 additional markers were also found to be highly significantly differentially expressed by ATCs and DTCs. Clustering and classification analysis based on the previously identified 8-marker transformation panel, or the 5 of these markers that were found to be most important in the current study, readily separated DTC and ATC with a high degree of accuracy.

The markers observed to change during thyroid cancer progression validate prior observations and represent promising molecular diagnostic or prognostic tools and identify targets for therapy of ATC.