Bordi C
Department of Pathology and Laboratory Medicine, Anatomic Pathology Section, University of Parma, I-43100 Parma, Italy.
Dig Liver Dis. 2004 Feb;36 Suppl 1:S31-4. doi: 10.1016/j.dld.2003.11.011.
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.
本文综述了与两种主要的多发性内分泌腺瘤（MEN）综合征（1型和2型）相关的肿瘤的病理变化，以及它们与导致个体综合征的基因缺陷之间的关系。与MEN 1相关的肿瘤主要影响垂体、甲状旁腺和胰腺，是由于位于11q13的MEN 1抑癌基因失活所致。尽管已知MEN 1综合征至少有一种特殊表型，但尚未揭示基因型与表型之间的关系。与MEN 2相关的肿瘤主要影响甲状腺C细胞、甲状旁腺和肾上腺髓质，是由于位于10q11.2的RET原癌基因的致癌点突变所致。MEN 2综合征的两种主要表型，即MEN 2A和MEN 2B，与RET癌基因的不同突变相关，这些突变大多位于MEN 2A的外显子10或11以及MEN 2B的外显子16的密码子918处。无论MEN疾病的类型如何，所有MEN靶器官中肿瘤的发生模式基本相似。初始病变是受影响的内分泌组织的弥漫性增生性增殖，双侧成对器官受累，随后发展为多个微结节，最终发展为大结节病变。这种内分泌增生性变化与肿瘤的关联提示在明显散发肿瘤的患者中存在MEN情况。对MEN 1病例的杂合性缺失（LOH）研究表明，每个多发性肿瘤都是独立遗传事件的结果。
