Tumor heterogeneity in a follicular carcinoma of thyroid: a study by comparative genomic hybridization

We report a follicular carcinoma of thyroid that showed a range of histologic appearances, with microfollicular, macrofollicular/pseudopapillary, oncocytic, and poorly differentiated areas. We used comparative genomic hybridization to detect the major DNA copy number changes in each component, in order to study the inter-relationships among them. All showed gains in 11q and 17q, suggesting that these were early events in the development of the tumor, and these were the only changes in the follicular component. The other components each showed additional gains and losses, some unique to one component. The oncocytic component showed most changes, including loss on 16q in the region of the E-cadherin gene. This was associated with reduced intensity of immunostaining for E-cadherin specifically in that component. No mutations in the E-cadherin gene were detected in this component. The demonstration that some DNA copy number changes are consistent across each component suggests that they are all clonally related. The additional chromosomal and immunohistochemical heterogeneity across the macrofollicular/pseudopapillary, oncocytic, and poorly differentiated components would be consistent with the emergence of subclones, possibly as part of tumor progression.