CLONAL ORIGIN OF PITUITARY-ADENOMAS
CLONAL ORIGIN OF PITUITARY-ADENOMAS
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DOI：
10.1210/jcem-71-6-1427
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发表时间：
1990-12-01
影响因子：
5.8
通讯作者：
MELMED, S
中科院分区：
文献类型：
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作者：
HERMAN, V;FAGIN, J;MELMED, S
由于垂体腺瘤的发病机制尚不清楚，我们对常见肿瘤的克隆组成进行了研究。通过分析X染色体基因次黄嘌呤磷酸核糖转移酶和磷酸甘油酸激酶的限制性片段长度多态性及其各自的甲基化模式，确定女性患者的克隆性。对62例女性垂体腺瘤经蝶手术患者进行外周血淋巴细胞DNA筛查。11例患者为PGK上的Bgl I位点杂合，4例为HPRT上的BamHI位点杂合，1例为两个位点杂合。在这16例患者中，3例患有肢端肥大症，4例患有库兴氏病，7例患有高泌乳素血症，2例临床无功能。手术后，形态学研究，包括免疫组织化学和病理标本的电子显微镜，允许克隆性和肿瘤细胞类型之间的直接比较。对照新鲜正常垂体组织发现是多克隆的。以下肿瘤是单克隆的：所有3个生长激素腺瘤，4个催乳激素肿瘤，3个促肾上腺皮质激素细胞腺瘤，促性腺激素腺瘤和非分泌性腺瘤。一个混合性多激素腺瘤是多克隆的，2个肿瘤由腺瘤性催乳细胞和非肿瘤性腺垂体垂体组织组成，1个促肾上腺皮质激素腺瘤和正常垂体组织混合。功能性垂体腺瘤来源于生长激素细胞、促肾上腺皮质激素细胞或催乳激素细胞和非分泌性肿瘤，本质上是单克隆的，这表明体细胞突变先于这些细胞的克隆性扩增，在垂体肿瘤发生中起主要作用。
As the pathogenesis of pituitary adenomas remains unclear, the tumor clonal composition of the common neoplasms was studied. Clonality was determined in female patients by analysis of restriction fragment length polymorphisms of the X-chromosome genes hypoxanthine phosphoribosyl transferase and phosphoglycerate kinase in conjunction with their respective methylation patterns. Peripheral lymphocyte DNA was screened from 62 female patients undergoing transsphenoidal surgery for pituitary adenoma. Eleven patients were heterozygous for the BglI site on PGK, 4 for the BamHI site on HPRT, and 1 patient for both sites. Of these 16 patients, 3 had acromegaly, 4 had Cushing''s disease, 7 had hyperprolactinemia, and 2 were clinically nonfunctional. After surgery, morphological study, including immunohistochemistry and electron microscopy of the pathological specimens, allowed a direct comparison between clonality and tumor cell type. Control fresh normal pituitary tissue was found to be polyclonal. The following tumors were monoclonal: all 3 somatotroph adenomas, 4 of 4 lactotroph tumors 3 of 4 corticotroph cell adenomas, a gonadotroph adenoma, and a nonsecretory adenoma. A mixed plurihormonal adenoma was polyclonal, as were 2 tumors consisting of adenomatous lactotrophs interspersed with nontumorous adenohypophyseal pituitary tissue and one corticotroph adenoma mixed with normal pituitary tissue. Functional pituitary adenomas derived from somatotrophs, corticotrophs, or lactotrophs and nonsecretory tumors are monoclonal in nature, suggesting that somatic cell mutations preceed clonal expansion of these cells and play a major role in pituitary tumorigenesis.