THYROID-STIMULATING HORMONE PROMOTES GROWTH OF THYROID CARCINOMAS IN TRANSGENIC MICE WITH TARGETED EXPRESSION OF THE RET PTC1 ONCOGENE/

Thyroid carcinomas from mice bearing a thyroid-targeted ret/PTC1 oncog ene were studied for responsiveness to endogenous thyroid-stimulating hormone (TSH) to evaluate the effect of TSH on tumor progression. Mice of both sexes were maintained for either 3 or 6 months on a low-iodin e diet (LID;<0.05 ppm) to decrease thyroid hormone production and incr ease endogenous pituitary TSH secretion. Nontransgenic littermates ser ved as controls. Lesions in mice on LID were observed only in the thyr oid and pituitary glands. LID induced marked hyperplasia of thyroid fo llicular cells of nontransgenic control mice at both time points despi te a return of TSH levels to normal values after 6 months of treatment . All transgenic mice had bilateral thyroid carcinomas with histologic features resembling human papillary thyroid carcinoma. The LID result ed in a progressive increase in thyroid area weight and tumor cellular ity with the development of a prominent spindle-cell component in the thyroid carcinomas after 6 months. There was no evidence, however, of local or distant metastasis of the thyroid carcinomas. Despite the lac k of histologic differentiation, the spindle-cell population retained focal immunoreactivity for thyroglobulin. Our results show that ret/PT C1-induced thyroid follicular cell carcinomas retain TSH responsivenes s and maintain a benign biologic behavior despite histologic evidence of anaplasia.