1. Genetic and Biological Subgroups of Low-Stage Follicular Thyroid Cancer
- Author
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French, Christopher A., Alexander, Erik K., Cibas, Edmund S., Nose, Vania, Laguette, Julia, Faquin, William, Garber, Jeff, Moore, Francis, Fletcher, Jonathan A., Larsen, P. Reed, and Kroll, Todd G.
- Abstract
Investigations of cancer-specific gene rearrangements have increased our understanding of human neoplasia and led to the use of the rearrangements in pathological diagnosis of blood cell and connective tissue malignancies. Here, we have investigated 3p25 rearrangements of the peroxisome proliferator-activated receptor γ(PPARγ) gene in follicular epithelial tumors of the human thyroid gland. Eleven of 42 (26%) low-stage follicular carcinomas, 0 of 40 follicular adenomas, 1 of 30 Hurthle cell carcinomas, 1 of 90 papillary carcinomas, and 0 of 10 nodular goiters had 3p25 rearrangements by interphase fluorescence in situhybridization. All 11 follicular carcinomas with 3p25 rearrangement exhibited strong, diffuse nuclear immunoreactivity for PPARγ, consistent with expression of PPARγ fusion protein. Twelve of 42 (29%) low-stage follicular carcinomas had 3p25 aneusomy without PPARγrearrangement (P= 0.01), suggesting that PPARγrearrangement and aneuploidy are independent early events in follicular cancer. Eleven of 12 follicular carcinomas with 3p25 aneusomy exhibited no PPARγ immunoreactivity, supporting the existence of two independent pathways. Follicular carcinoma patients with PPARγrearrangement more frequently had vascular invasion (P= 0.01), areas of solid/nested tumor histology (P< 0.001), and previous nonthyroid cancers (P< 0.01) compared with follicular carcinoma patients without PPARγrearrangement. Our experiments identify genetic subgroups of low-stage follicular thyroid cancer and provide evidence that follicular carcinomas with PPARγrearrangement are a distinct biological entity. The findings support a model in which separate genetic alterations initiate distinct pathways of oncogenesis in thyroid carcinoma subtypes.
- Published
- 2003
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