Expression of PRAD1 cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma
Expression of PRAD1 cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma
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DOI：
10.1046/j.1523-1755.1999.00396.x
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发表时间：
1999-04-01
影响因子：
19.6
通讯作者：
Takagi, H
中科院分区：
文献类型：
--
作者：
Tominaga, Y;Tsuzuki, T;Takagi, H
背景在原发性甲状旁腺功能亢进症中，某些遗传异常被认为是甲状旁腺肿瘤发生的原因，据报道，由甲状旁腺激素（PTH）基因的DNA重排诱导的PRAD 1/细胞周期蛋白D1的过度表达是许多原发性甲状旁腺腺瘤中的遗传疾病之一。然而，在尿毒症引起的继发性甲状旁腺功能亢进中，结节性甲状旁腺增生的单克隆增殖机制尚不清楚。为了阐明其机制，我们检测了PRAD 1/cyclin D1、视网膜母细胞瘤基因产物和Ki 67在原发性腺瘤和继发性增生中的表达。在原发性甲状旁腺功能亢进患者的腺瘤（N = 15）和相关腺体（N = 7）中，以及因肾性甲状旁腺功能亢进而接受甲状旁腺切除术的患者的弥漫性（N = 14）、多结节性（N = 58）和单个结节性（N = 28）腺体中，通过免疫组织化学技术评价这些细胞周期调节因子的表达。用标记指数来定义每种抗体核染色阳性的细胞比例。在15例原发性腺瘤中，有6例（40%）PRAD 1/细胞周期蛋白D1过表达（标记指数超过500），可能是因为PTH基因重排，但在继发性增生（包括单个结节性腺体）中不表达。与弥漫性增生相比，结节性增生中PRAD 1/cyclin D1（P < 0.05）、视网膜母细胞瘤基因产物（P < 0.05）和Ki 67（P < 0.05）的表达明显增高。PRAD 1/cyclin D1与Ki 67在原发性腺瘤和继发性增生中的表达无明显相关性。这些结果表明，在继发性增生引起的尿毒症，至少显着的过度表达PRAD 1/细胞周期蛋白D1的PTH基因重排诱导可能不是主要的遗传异常负责肿瘤的发生。异质性遗传变化似乎有助于PRAD 1/细胞周期蛋白D1的表达或其他一些独立于原癌基因扩增的机制诱导的甲状旁腺细胞的单克隆增殖。
Background In primary hyperparathyroidism, certain genetic abnormalities responsible for parathyroid tumorigenesis are proposed, and it has been reported that the overexpression of PRAD1/cyclin D1 induced by a DNA rearrangement of the parathyroid hormone (PTH) gene is one of the genetic disorders in a number of primary parathyroid adenomas. However, in secondary hyperparathyroidism caused by uremia, the mechanism of monoclonal proliferation in nodular parathyroid hyperplasia is not well understood. To elucidate the mechanism, we examined the expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in primary adenoma and secondary hyperplasia.Methods. In adenomas (N = 15) and associated glands (N = 7) with normal histology obtained from patients with primary hyperparathyroidism and in diffuse (N = 14), multinodular (N = 58), and single nodular (N = 28) glands from patients who underwent parathyroidectomy for renal hyperparathyroidism, the expression of these cell cycle regulators was evaluated by immunohistochemical technique. A labeling index was used to define the proportion of cells with positive nuclear staining by each antibody.Results. In 6 out of 15 (40%) primary adenomas, PRAD1/cyclin D1 was overexpressed (a labeling index of more than 500), possibly because of the PTH gene rearrangement, but not in secondary hyperplasia, including single nodular glands. Compared with diffuse hyperplasia, nodular hyperplasia showed a significantly higher expression of PRAD1/cyclin D1 (P < 0.05), retinoblastoma gene products (P < 0.05), and Ki67 (P < 0.05). However, no statistically significant correlation between the expression of PRAD1/cyclin D1 and that of Ki67 was observed in both primary adenoma and secondary hyperplasia.Conclusions. These results suggest that in secondary hyperplasia caused by uremia, at least remarkable overexpression of PRAD1/cyclin D1 induced by PTH gene rearrangement may be not the major genetic abnormality responsible for tumorigenesis. Heterogenous genetic changes seem to contribute to monoclonal proliferation of parathyroid cells induced by the expression of PRAD1/cyclin D1 or by some other mechanism independent of the amplification of the proto-oncogene.