Clonal origins of adrenocorticotropin-secreting pituitary tissue in Cushing's disease.
Clonal origins of adrenocorticotropin-secreting pituitary tissue in Cushing's disease.
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DOI：
10.1210/jcem.75.5.1358909
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发表时间：
1992-11
期刊：
影响因子：
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通讯作者：
B. Biller;J. Alexander;N. Zervas;E. Hedley‐Whyte;A. Arnold;A. Klibanski
中科院分区：
文献类型：
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作者：
B. Biller;J. Alexander;N. Zervas;E. Hedley‐Whyte;A. Arnold;A. Klibanski
库欣氏病是原发性垂体功能紊乱引起的还是下丘脑对垂体控制异常引起的尚不清楚。克隆分析可以提供关于肿瘤组织是否来源于遗传改变的细胞的单克隆增殖或来源于受共同刺激影响的一组细胞的多克隆扩增的信息。我们在11名经生化和病理证实的库欣病妇女中，采用磷酸甘油酸激酶、次黄嘌呤磷酸核糖转移酶和DXS 255位点的X-连锁限制性片段长度多态性来确定促肾上腺皮质激素腺瘤和促肾上腺皮质激素增生的克隆起源。所有10例经形态学和免疫化学证实的ACTH分泌型垂体微腺瘤的肿瘤组织均表现为单克隆模式。在一例分泌CRH的支气管类癌患者中，病理证实促肾上腺皮质激素细胞增生是多克隆的。我们的结论是，在库欣病促肾上腺皮质激素微腺瘤是单克隆的，支持的理论，自发体细胞突变是主要的发病机制，在这种疾病。此外，促肾上腺皮质激素细胞增生的多克隆性表明下丘脑激素过多是与异位CRH分泌肿瘤相关的库欣综合征病例的病因机制。
It is unclear whether Cushing's disease results from a primary pituitary disorder or arises in response to abnormal hypothalamic control of the pituitary gland. Clonal analysis can provide information as to whether neoplastic tissue is derived from a monoclonal proliferation of a genetically altered cell or from a polyclonal expansion of a group of cells affected by a common stimulus. We used X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase, hypoxanthine phosphoribosyltransferase, and DXS255 loci in 11 women with biochemically and pathologically confirmed Cushing's disease to determine the clonal origins of corticotroph adenomas and corticotroph hyperplasia. Tumor tissue from all 10 women with morphologically and immunohistochemically confirmed ACTH-secreting pituitary microadenomas demonstrated a monoclonal pattern. Pathologically confirmed corticotroph hyperplasia in a patient with a CRH-secreting bronchial carcinoid was found to be polyclonal. We conclude that corticotroph microadenomas in Cushing's disease are monoclonal, supporting the theory that a spontaneous somatic mutation is the primary pathogenetic mechanism in this disorder. In addition, the demonstration of polyclonality in corticotroph hyperplasia implies that excess of hypothalamic hormones is an etiologic mechanism in cases of Cushing's syndrome associated with ectopic CRH-secreting tumors.