Endocrine Abstracts

While primary hyperparathyroidism is most commonly due to a parathyroid adenoma, very occasionally it may be secondary to a parathyroid carcinoma. A substantial minority of parathyroid adenomas are due to mutations or transpositions in genes in involved in the regulation of the cell cycle. In particular, at the cell cycle checkpoint which regulates exit from G1 phase, there is an interaction between the cyclins and cyclin-dependent kinases (CDKs); specifically, cyclin D interacts with CDK4 and CDK6, while cyclin E primarily regulates CDK2. Activation of CDKs leads to phosphorylation of Rb protein, which allows the cell to proceed past the checkpoint into mitosis. There are a number of inhibitors of the CDKs, particularly p27, which principally blocks the interaction of cyclin E with CDK2. We have now investigated whether expression of certain of the cell cycle regulators are differentially expressed in parathyroid adenomas and carcinomas compared to normal parathyroid tissue, and how they relate to a marker of cell proliferation, Ki-67.
We chose a panel of paraffin-embedded parathyroid adenomas (n=29) and carcinomas (n=21), and normal parathyroid tissue (n=10), and performed immunohistochemical staining for cyclin D1, Rb and p27 and Ki-67 using the standard ABC technique. This was quantified counting positive nuclei per section, scoring blind the tissue as positive or negative, and comparing the tissues by non-parametric statistical tests.
Ki-67 expression was significantly higher in carcinomas compared to either the adenomas (P=0.0329) or normal tissue (P=0.0177). Both Rb and p27 showed a progressive fall in immunopositivity from normal to adenoma to carcinoma tissue. Cyclin D1 expression was equally elevated in the adenoma and carcinoma cases compared to the normal tissue.
It is concluded that Ki-67 expression shows a progressive increase in moving from adenomas to carcinomas, and that this is directly paralleled by significant down-regulation in Rb and p27 protein expression.