Matrix metalloproteinases and tissue inhibitors of metalloproteinases in thyroid C-cells and medullary thyroid carcinomas

Aims : Hyperplastic C-cells of the thyroid and medullary thyroid carcinomas (MTCs) were studied immunocytochemically for calcitonin, carcinoembryonic antigen (CEA), chromogranin A, matrix metalloproteinase (MMP)-2 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 and -2. Methods and results : Non-neoplastic C-cells were positive for all these substances whereas MTC tumour cells were relatively weaker stained, and thyroid follicular cells were negative for all the substances studied. We have recently reported that pancreatic islet cells and islet cell tumours were positive for MMPs and TIMPs, and, in addition, anterior pituitary cells and pituitary adenomas and parathyroid gland and its adenomas were also positively stained. The MMP- and TIMP-positive endocrine cells correspond to Pearse's APUD cells, derived from neural crest and endodermal cells. Conclusions : MMPs and TIMPs may well be added as newly recognized markers for neuroendocrine cells. The possible function of MMP-TIMP homeostasis in C-cells and MTCs is discussed.