ANALYSIS OF PROLIFERATIVE ACTIVITY OF THE PARATHYROID-GLANDS USING PROLIFERATING CELL NUCLEAR ANTIGEN IN PATIENTS WITH HYPERPARATHYROIDISM

To elucidate the cellular proliferative kinetics of the parathyroidal gland in patients with hyperparathyroidism, we investigated the expres sion of proliferating cell nuclear antigen (PCNA) in parathyroidal tis sues using an immunohistochemical procedure. The PCNA labeling index ( LI; maximum LI, maximal stained area; average LI, evenly distributed s tained area) indicating cellular proliferative activity was defined as the number of PCNA-positive cells per 1000 parathyroid cells in the r egion of interest. We used these indexes to compare and investigate th e proliferative activity of parathyroid cells under various conditions . The specimens used for the study were 42 parathyroid glands from 21 patients with primary hyperparathyroidism (19 cases of adenoma and 2 c ases of primary hyperplasia due to multiple endocrine neoplasia type 1 ) and 129 parathyroid glands from 32 patients with secondary hyperpara thyroidism. An additional 40 parathyroid glands resected during thyroi d surgery of 30 normocalcemic patients were used as normal controls. I n normally functioning parathyroids, a small number of cells in the gr owth phase were found. In primary hyperparathyroidism, proliferative a ctivity was highest in the adenoma followed by primary hyperplasia. In contrast, the PCNA LIs showed a low value in the normal rim of the ad enoma and normal glands resected as biopsy specimens from adenoma pati ents. We, therefore, assumed that proliferative activity was suppresse d in these cells compared with that in normally functioning glands. In secondary hyperparathyroidism, when the cell component of the parathy roid tissues was divided into five types, PCNA immunoreactivity was lo west in the dark chief cells. Proliferative activity in cells of the o xyphil series was the same or higher than that in the clear chief cell s or vacuolated chief cells. When classified according to the structur e of the parathyroid glands, cell proliferation was significantly high er in the nodular type than in the diffuse type (maximum LI, 176 +/- 2 31 vs. 38.3 +/- 55.7; average LI, 120 +/- 188 vs. 24.8 +/- 43.5; mean +/- SD; P < 0.001). More PCNA-immunoreactive cells were found in autot ransplanted glands with recurrence than in glands resected during the initial surgery. To summarize the PCNA expression classified according to the pathological types of hyperparathyroidism, the PCNA LIs were h ighest in secondary hyperplasia (maximum LI, 144 +/- 212; average LI, 96.0 +/- 169) and adenoma (maximum LI, 102 +/- 81.7; average LI, 67.5 +/- 67.7), followed by primary hyperplasia (maximum LI, 25.0 +/- 25.4; average LI, 19.2 +/- 22.2) and normal glands (maximum LI, 13.6 +/- 23 .9; average LI, 4.40 +/- 8.90). These findings suggest that the cellul ar proliferative kinetics of the parathyroid gland differ depending on the type of hyperparathyroidism, glandular structure, and cell compon ents. As the detection method of intranuclear expression of PCNA in ce lls is too sensitive, we should be careful not to overestimate the num ber of cells in the proliferative cycle. However, these results could not have been obtained using a conventional method such as DNA analysi s by flow cytometry.