Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study.
Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study.
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DOI：
10.1210/jcem.81.5.8626826
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发表时间：
1996-05
期刊：
影响因子：
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通讯作者：
E. Hsi;L. Zukerberg;W. Yang;A. Arnold
中科院分区：
文献类型：
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作者：
E. Hsi;L. Zukerberg;W. Yang;A. Arnold
细胞周期蛋白D1(PRAD1)癌基因与甲状旁腺激素基因重排，并在甲状旁腺腺瘤中转录激活。由于重排断裂点的异质性，细胞周期蛋白D1缺失的腺瘤的真实百分比尚不清楚。在甲状旁腺腺瘤中，细胞周期蛋白D1蛋白的过度表达似乎是所有细胞周期蛋白D1基因重排的统一结果，因此，可以用来更全面地识别细胞周期蛋白D1在其中起重要作用的腺瘤。应用微波增强免疫组织化学方法和亲和纯化的细胞周期蛋白D1多克隆抗血清，对65例甲状旁腺腺瘤、51例正常甲状旁腺和4例甲状旁腺癌组织中细胞周期蛋白D1的表达进行了研究。当可用时，还收集了腺瘤质量、完整的甲状旁腺激素水平和同时存在的血钙水平的数据。65个腺瘤中有12个(18%)显示约30-70%的肿瘤细胞呈弥漫性核染色。51个正常腺体均为阴性，仅1个腺体可见散在细胞(<；10%)，核染色阳性。此外，在2例细胞周期蛋白D1阴性的腺瘤周围正常甲状旁腺组织的受压边缘可见散在的阳性细胞。在阳性和阴性肿瘤之间，腺瘤质量、完整的甲状旁腺激素水平或并发钙水平没有显著差异。2例患者的4例甲状旁腺癌标本中有2例细胞周期蛋白D1呈强核染色。由于细胞周期蛋白D1/甲状旁腺激素易位和/或其他机制，我们的病例中有18%的病例中有细胞周期蛋白D1的过度表达，这表明细胞周期蛋白D1的过度表达在甲状旁腺腺瘤的发病机制中所起的作用比先前所认识的要大得多。细胞周期蛋白D1的过度表达是典型的甲状旁腺腺瘤的一个特征，并不局限于早期DNA研究所提示的异常大的、引起症状的腺瘤。虽然只有三名甲状旁腺癌患者被研究，但其中两名患者的肿瘤细胞周期蛋白D1染色，这增加了细胞周期蛋白D1在肿瘤中过度表达的可能性。细胞周期蛋白D1的过度表达似乎突出了甲状旁腺肿瘤的一条中心通路。
The cyclin D1 (PRAD1) oncogene is rearranged with the PTH gene and is transcriptionally activated in a subset of parathyroid adenomas. Because of heterogeneity in rearrangement breakpoints, the true percentage of adenomas with cyclin D1 deregulation is unknown. Overexpression of the cyclin D1 protein in parathyroid adenomas appears to be a unifying consequence of all cyclin D1 gene rearrangements and can, therefore, be examined to more comprehensively identify adenomas in which cyclin D1 is pathogenetically important. We studied cyclin D1 expression in 65 parathyroid adenomas (from 64 patients), 51 normal parathyroid glands (from the same patients), and 4 parathyroid carcinoma specimens (from 3 patients) using a microwave-enhanced immunohistochemical method and affinity-purified cyclin D1 polyclonal antiserum. When available, data on adenoma mass, intact PTH level, and concurrent serum calcium level were also collected. Twelve of the 65 adenomas (18%) showed diffuse nuclear staining of approximately 30-70% of the tumor cells. All 51 normal glands were negative, except 1 gland that showed scattered cells ( < 10%) with positive nuclear staining. In addition, scattered positive cells were seen in the compressed rim of histologically normal parathyroid tissue surrounding 2 adenomas that were cyclin D1 negative. No significant differences in adenoma mass, intact PTH levels, or concurrent calcium levels were found between positive and negative tumors. Two of 4 parathyroid carcinoma specimens from 2 of 3 patients showed strong nuclear staining for cyclin D1. Overexpression of the cyclin D1 oncogene in 18% of our cases, due to the cyclin D1/PTH translocation and/or other mechanisms, suggests that overexpressed cyclin D1 plays a role in the pathogenesis of a much larger proportion of parathyroid adenomas than previously appreciated. Cyclin D1 overexpression is a feature of typical parathyroid adenomas and is not confined to unusually large, symptom-causing adenomas as had been suggested by early DNA studies. Although only three patients with parathyroid carcinoma were studied, two of the patients' tumors stained for cyclin D1, raising the possibility that the frequency of cyclin D1 overexpression may be even greater in carcinomas. Cyclin D1 overexpression appears to highlight a central pathway in parathyroid neoplasia.