Abstract :
In spite of the generally benign phenotype of parathyroid neoplasms, several of the mechanisms of tumor biology are applicable to parathyroid tumorigenesis. The molecular mechanisms which underlie parathyroid tumor development start to be recognized. The possibility of evaluating four distinct organs greatly contributed to the knowledge of the genetic bases of parathyroid tumorigenesis.
Growth factors could act as extrinsic proliferative agents in early parathyroid tissue polyclonal proliferation, preceeding and even promoting successive irreversible mutations. A systemic growth stimulating substance has been described in plasma of patients affected by multiple endocrine neoplasia type 1 (MEN 1) syndrome. Overexpression of the PRAD1 oncogene encoded protein, a cell cycle regulator is typical of a small subset of parathyroid tumors, while activation of ras proto-oncogene could not be detected in a large series of parathyroid lesions. Moreover, analysis of mutation of the ret proto-oncogene, commonly associated with parathyroid neoplasia in MEN 2A, is uncommon in parathyroid tumors.
Loss of heterozygosity on chromosoma 11q13, which implies deletion of a tumor suppressor gene on this chromosomal region, occurs in sporadic parathyroid adenomas and more frequently in parathyroid tumors in patients with familial MEN 1 syndrome. Inactivation of the RB tumor suppressor gene has been described in a large subset of parathyroid carcinomas, suggesting its role in the molecular pathogenesis of malignant progression of parathyroid tumors. Allelic losses in parathyroid carcinomas were also demonstrated for p53, whose encoded product is known to regulate the cell cycle at the G1/S transition.
It is apparent that even if a discrete number of genetic mechanisms of parathyroid tumorigenesis has been uncovered, the concept of successive mutations has yet to be proven for parathyroid neoplasms. We are confident that in the future special features of parathyroid tumorigenesis (rarity, dependence on neck irradiation, loss of calcium control) will find an answer.
