THE MECHANISM OF THE DEVELOPMENT OF PARATHYROID CANCERS - A ROLE OF PARATHYROID HORMONE-RELATED PROTEIN

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We investigated the expression of parathyroid hormone-related protein (PTHrP) in hyperplasia cases, adenomas and carcinomas of the human parathyroid glands. In hyperplasia cases with nodule formation, there were different types of nodules in the hyperplastic glands. Some nodules were strongly expressed PTHrP, while others were negative. The cell growth activity was significantly suppressed in PTHrP positive nodules, suggesting that PTHrP has a close relationship with cell growth suppression. Then, we compared PTHrP expression in 10 adenomas and 21 carcinomas of the parathyroids. Both the frequency and the intensity of PTHrP expression were significantly suppressed. The cell growth activity of parathyroid carcinoma is higher than that in adenomas. Therefore, suppressed PTHrP expression in carcinomas may related to the development of parathyroid carcinomas. It is reported that rearrangement of Cyclin D1 gene with PTH gene causes parathyroid adenoma. We studied Cyclin D1 expression in hyperplasia cases, adenomas, and carcinomas of the parathyroids. Cyclin D1 expression was more frequently found in both hyperplasia cases and carcinomas than in adenomas. There was one extremely rare case of parathyroid carcinoma in a series of our study. The cases was that parathyroid carcinoma arising in the background of secondary hyperplasia in a patient with long-term hemodialysis. The density of Cyclin D1 positive cells was significantly higher in carcinomatous area. Thus, Cyclin D1 must have an important role in the development of parathyroid carcinoma.