Parathyroid glands in uraemic patients with refractory hyperparathyroidism: histopathology and p53 protein expression analysis

Refractory hyperparathyroidism is a state of parathyroid hyperfunction and hypercalcaemia in uraemic patients with previous secondary hyperplasia. We studied histopathological features and p53 expression in 49 parathyroid glands of uraemic patients (n = 21) with refractory hyperparathyroidism in order to investigate whether p53 abnormalities could be present in parathyroid hyperplasias of chronic renal failure. Nodular hyperplasia was found in 77.5% of the glands (n = 38). The proportion of oxyphil cells and acinar cell arrangements was higher in nodular hyperplasia than in diffuse hyperplastic glands P < 0.001). Duration of renal disease and haemodialysis treatment tended to be longer in patients with nodular hyperplasia. There was no correlation between serum intact PTH (iPTH), calcium and hyperplasia pattern. A trend for a higher glandular mass was found in nodular type hyperplasia (1.88 +/- 2.13 g) than in diffuse type hyperplasia (0.87 +/- 1.28 g; P = 0.06). Nuclear p53 immunoreactivity was shown in 55% of the hyperplastic glands, whereas it was not detected in 12 normal parathyroid glands used as controls. p53 staining was present in c. 82% of the diffuse hyperplastic glands and in 47% of the nodular hyperplastic glands (P = 0.08). Nodular type hyperplasia was the predominant histopathological pattern in uraemic patients with refractory hyperparathyroidism in our study. Nodular hyperplastic glands characteristically had higher percentage of oxyphil cells, acinar cell arrangements and mass than diffuse hyperplastic glands. A high prevalence of p53 protein expression was found in hyperplastic glands of uraemic patients. Our results suggest that p53 abnormalities might be involved in the pathogenesis of parathyroid hyperplasia in chronic renal failure.