The profile of ErbB/Her family genes copy number assessed by real-time PCR in parathyroid adenoma and hyperplasia associated with sporadic primary hyperparathyroidism.

Abstract

Hyperparathyroidism (pHPT) is a relatively frequent endocrinopathy, however, the molecular mechanisms of its etiology remain poorly understood. This disorder is mainly associated with benign tumours (adenoma) and hyperplasia of the parathyroid, hence, the focus is directed also to genes that are likely to be involved in carcinogenesis. Among such genes are ErbB/Her family genes already used in diagnosis of other tumours (e.g., breast carcinoma) and reported also to play a role in development of endocrine lesions. So far, ErbB-1/Her-1/EGFR expression has been detected in pHPT-associated adenomas and hyperplasia as opposed to no expression in normal parathyroid tissue. Moreover, losses or gains of the fragments of chromosomes where ErbB/Her genes are located have been reported. In this study, the gene dosage of ErbB/Her family genes were determined for the first time in parathyroid adenomas, hyperplasia and morphologically unchanged tissue in order to establish their putative role in the development of the disease. Genomic DNA was isolated from 33 patients with sporadic hyperparathyroidism and the gene copy numbers were assessed using real-time PCR. The ErbB/Her genes' profile was unaltered in most of the examined samples. Two low-level amplifications of ErbB-1/Her-1/EGFR gene, two deletions of ErbB-2/Her-2, and six deletions of ErbB-4/Her-4 were found. The ErbB-3/Her-3 gene remained unaffected. No correlation with clinical parameters was found for any gene. Both the low number of alterations and a lack of their associations with clinical parameters exclude the prognostic value of the ErbB/Her genes family in parathyroid tumourigenesis. Nevertheless, the ErbB-4/Her-4 deletions seem to be interesting for further investigations, especially in the context of PTH secretion.