Molecular profile of parathyroid tissues and tumours: a heterogeneous landscape.

Abstract

Advances in laboratory diagnostics and surgical treatment ofprimary hyperparathyroidism have ensured solid basis for research in parathyroid pathology in order to specify key molecules in pathogenesis and morphological diagnostics ofdifficult cases. Theaim ofthis study was to assess themolecular landscape and its heterogeneity in primary parathyroid hyperplasia (PPH) and adenoma, compared to carcinoma and normal glands. In aretrospective analysis of179 surgically removed parathyroid glands (102 adenomas; 27 PPH; 45 normal glands; 5 carcinomas), expression ofKi-67, p21, p27, p53, cyclin D1, Bcl-2 protein, vimentin, cytokeratin (CK) 19, E-cadherin, CD56, CD44 and parafibromin was detected by immunohistochemistry, followed by computer-assisted assessment ofmean values and heterogeneity measures. Descriptive statistics and Kruskal-Wallis test were applied. Significant differences were disclosed regarding themean and highest fraction ofKi-67 (both p < 0.001), p21 (both p < 0.001), cyclin D1 (p = 0.002) and p27-expressing cells (p = 0.010). Proliferative lesions (PPH, adenoma and carcinoma) showed statistically significantly up-regulated CK19 (p = 0.012), decreased E-cadherin levels and distinctive patterns ofvimentin. CD44, CD56 and p53 were almost absent from parathyroid tissues. All carcinomas lacked parafibromin contrasting with invariable positivity in adenomas. Remarkable heterogeneity ofcell cycle markers and intermediate filaments must be accounted for in scientific studies and elaboration ofdiagnostic cut-offs.