Multiple endocrine neoplasia (MEN)-associated tumours.
The pathological changes of tumours associated with the two main MEN syndromes, types 1 and 2, and their relation with the genetic defects responsible for the individual syndromes are reviewed. MEN 1-associated tumours, affecting mainly the pituitary, the parathyroids and the pancreas, are due to inactivation of the MEN 1 oncosuppressor gene located in 11q13. Although at least one peculiar phenotype of MEN 1 syndrome is known, no genotype-phenotype relation has been disclosed. MEN 2-associated tumours, affecting mainly the thyroid C cells, the parathyroids and the adrenal medulla, are due to oncogenic point mutations of the RET proto-oncogene located in 10q11.2. The two main phenotypes of the MEN 2 syndrome, known as MEN 2A and MEN 2B, are associated with different mutations of the RET oncogene, mostly located on exons 10 or 11 in MEN 2A and in codon 918 of exon 16 in MEN 2B. Independent of the type of MEN disease, the development of tumours follows a substantially similar pattern in all MEN target organs. The initial lesion is a diffuse hyperplastic proliferation of the affected endocrine tissue with bilateral involvement of pair organs, followed by development of multiple micro- and, eventually, macronodular lesions. Such association of endocrine hyperplastic changes and tumours is suggestive of a MEN condition in patients with apparently sporadic tumours. LOH investigations in MEN 1 cases indicate that each multiple tumour is the result of an independent genetic event.
Bordi
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Department of Pathology and Laboratory Medicine, Anatomic Pathology Section, University of Parma, I-43100 Parma, Italy. cesare.bordi@unipr.it
D006801:Humans; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics* / Q000473:pathology; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000473:pathology; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics*; D000090063:Proto-Oncogene Mas