CALCITONIN SECRETION, C-CELL-DIFFERENTIATION AND PROLIFERATION DURINGTHE SPONTANEOUS DEVELOPMENT OF MURINE MEDULLARY-THYROID CARCINOMA

Medullary thyroid carcinoma (MTC), a C cell neoplasm, synthesizes larg e amounts of calcitonin (CT), its biological market. However. in some cases with a poor prognosis, MTC is associated with low basal CT level s owing to a decrease in the thyroid CT content. Using a murine model of human MTC, we studied the relationships between CT biosynthesis. C cell proliferation, and the circulating CT level during MTC: progressi on, Cell proliferation was revealed by autoradiography of radioactive thymidine incorporation in dividing nuclei, after CT or CT mRNA detect ion by immunocytochemistry (ICC) or ill situ hybridization (ISH). All rat thyroids showed a severe hyperplasia of C cells containing signifi cant amounts of CT and CT mRNA, and a very low mitotic index. Tumours were found in 68% of the thyroids. In the strongly immunoreactive smal l nodules (ICC+), many labelled nuclei were observed. Subsequently som e nodular cells, still containing detectable CT mRNA (ISH+), were not detected by immunochemistry (ICC-) owing to a dramatic decrease in sec retory granules, Their mitotic index increased. and a rise of the basa l CT plasma level was noted. These ISH+, ICC- tumour MTC cells cells r epresent a modified aggressive tumour C cell population exhibiting an increased ability to proliferate and were detected by the rise in the basal circulating CT level.