Clonarity analysis on hyperparathyroidism

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Purpose : To differentiate between morioclonal neoplasia and polyclonal hyperplasia arising in the primary and secondary hyperparathyroidism (PHPT and SHPT) and to elucidate the molecular basis responsible for the neoplastic proliferation.Materials and Methods : The surgical materials of parathyroids obtained from the patients with PHPT and SHPT were investigated using molecular genetic analysis.Results : 1. The neoplastic lesion usually showed a homogeneous distribution of the PTH hormone versus heterogeneous in hyperplastic lesion in immunohistochemistry. 2. By X-linked PGK and HUMARA gene inactivation analysis, almost all of the parathyroid adenomas were demonstrated to be of monoclonal origin. Contrary to the traditional histological crieria, majority of the primary (2/2) and secondary multigland hyperplasia (19/27, 70.4%) were also of monoclonal origin. A progression from polyclonal hyperplasia to monoclonal neoplasia might be present in the development of SHPT.3. Different parath … More yroid disorders were related to different genetic abnormalities. 1). Not only in parathyroid carcinomas, but also in parathyroid adenomas, particularly those with nuclear pleomorphism, were detected overexpression of p53 protein (4/32), somatic mutation (R290H), polymorphism (L252L,R72P) and LOH.2). Abnormality of MEN 1 gene (W1 98X, A340T, A541T, T429K, D418D, V367V) was identified in both MEN 1 and sporadic endocrin tumors (parathyroid adenoma and pancreatic endocrine tumor), but only in less than 20% of parathyroid adenomas. 3). Different from MEN 1 gene, ret oncogene mutation seemed to be unrelated to parathyroid adenomas (0/16), although its somatic mutation was found in 32.5% (13/40) of thyroid medullary carcinoma. 4). In the parathyroids (20 glands) with SHPT, we have failed to find any abnormalities of p53, MEN 1 and 1 p35-36.Conclusion : 1. Parathyroid adenomas are of monoclonal origin, related to multiple genetic abnormalities. 2. Clonal analysis suggests a progression from polyclonal hyperplasia to monoclonal neoplasia in the SHPT with unknown genetic abnormality. 3. The distribution pattern of PTH hormone protein, clonality and genetic analysis are helpful in the differentiation between hyperplastic lesions and neoplasia. Less