Endocrine Abstracts

Background: Primary hyperparathyroidism represents the third most common endocrine pathology. Recently, the morphological classification of underlying parathyroid lesions underwent significant alterations: the former primary parathyroid hyperplasia was reclassified as multiglandular parathyroid disease (MPD), a term that is in line with clonality studies and surgeons’ needs; and the entity of atypical parathyroid tumour was separated from adenoma. Although the diagnostics of hyperparathyroidism is largely dependent on laboratory and radiological findings, pathological investigation of surgically removed glands can help to verify the diagnosis, to reach it in difficult cases and to assess the pathogenesis.

Aim: The aim of our study was to evaluate expression of cell cycle and apoptosis-related proteins in parathyroid adenoma and MPD in comparison to unequivocal parathyroid carcinoma and normal/atrophic glands.

Materials and methods: Expression of Ki-67, p21, p27, cyclin D1 and Bcl-2 were detected by immunohistochemistry and quantified (%) in adenomas (102) and MPD (27), compared to carcinoma (5) and normal glands (45). Descriptive statistics, Kruskal–Wallis test with Bonferroni correction and Mann–Whitney test were applied.

Results: The mean fraction of Ki-67 was 1.6% in adenomas and 1.0% in MPG, contrasting with 0.4% in normal glands and 5.8% in carcinoma; the highest values were in parallel: 3.4% vs 2.8% vs 1.0% vs 11.8%. p21 protein showed the highest expression in MPD (mean 15.7%; highest 29.8%), followed by adenoma (12.8%; 23.7%), carcinoma (7.6%; 15.6%) and normal glands (3.1%; 3.8%). Cyclin D1 levels in MPD (24.5%; 42.5%) exceeded the expression in adenoma (21.0%; 22.8%) although the levels were highest in carcinoma (31.5%; 41.8%) and low in normal tissues. Loss of p27 was significant only in carcinomas (59.0%), contrasting with 92.8% in adenomas, 94.3% in MPD and 97.9% in normal tissues. Similarly, loss of BCL2 was notable in carcinoma (28.2%), compared to adenoma (66.7%), MPD (61.3%) and normal glands (75.6%). Notably, nuclear markers showed remarkable heterogeneity by dense clusters of positive cells. Across all groups, significant differences were disclosed regarding the mean and highest fraction of Ki-67 (both P<0.001), p21 (both P<0.001), cyclin D1 (P=0.02) and p27-expressing cells (P=0.010). In contrast, adenomas, compared to MPD, featured higher proliferation but lower cyclin D1 levels; these groups did not differ by p27 and Bcl2.

Conclusion: The immunophenotype shows enhanced proliferation along with regulatory similarities between adenoma and multiglandular parathyroid disease, indicating pathogenetic links. Expression of cell cycle-related proteins in hyperfunctioning parathyroid tissues shows remarkable heterogeneity by dense clustering of positive cells, suggesting paracrine signalling mechanisms.