Clonarity analysis on hyperparathyroidism

目的：区分原发性和继发性甲状旁腺功能亢进（PHPT和SHPT）中发生的多克隆性增生和多克隆性增生，并阐明肿瘤增生的分子基础。材料与方法：对PHPT和SHPT患者的甲状旁腺手术材料进行分子遗传学分析。结果：1；在免疫组织化学中，肿瘤病变通常表现为PTH激素的均匀分布，而增生性病变则表现为不均匀分布。2. 通过x连锁PGK和HUMARA基因失活分析，几乎所有甲状旁腺瘤均为单克隆起源。与传统的组织学标准相反，大多数原发性（2/2）和继发性多腺增生（19/ 27,70.4%）也是单克隆起源。从多克隆增生到单克隆瘤变可能存在于shpt的发展过程中。更多的甲状腺疾病与不同的基因异常有关。1）. 不仅在甲状旁腺癌中，在具有核多形性的甲状旁腺瘤中，也检测到p53蛋白过表达（4/32）、体细胞突变（R290H）、多态性（L252L、R72P）和LOH.2)。MEN 1基因（W1 98X、A340T、A541T、T429K、D418D、V367V）异常在MEN 1和散发内分泌肿瘤（甲状旁腺瘤和胰腺内分泌肿瘤）中均有发现，但仅在甲状旁腺瘤中不到20%。3)。与MEN 1基因不同，ret癌基因突变似乎与甲状旁腺瘤无关（0/16），尽管其体细胞突变在32.5%（13/40）的甲状腺髓样癌中发现。4)。在SHPT的甲状旁腺（20个腺体）中，我们未发现p53， MEN 1和1 p35-36的异常。结论：1；甲状旁腺瘤是单克隆起源，与多种遗传异常有关。2. 克隆分析提示在遗传异常未知的SHPT中从多克隆增生到单克隆瘤变的进展。3. 甲状旁腺激素蛋白的分布规律、克隆性和遗传学分析有助于鉴别增生性病变和瘤变。少

Purpose : To differentiate between morioclonal neoplasia and polyclonal hyperplasia arising in the primary and secondary hyperparathyroidism (PHPT and SHPT) and to elucidate the molecular basis responsible for the neoplastic proliferation.Materials and Methods : The surgical materials of parathyroids obtained from the patients with PHPT and SHPT were investigated using molecular genetic analysis.Results : 1. The neoplastic lesion usually showed a homogeneous distribution of the PTH hormone versus heterogeneous in hyperplastic lesion in immunohistochemistry. 2. By X-linked PGK and HUMARA gene inactivation analysis, almost all of the parathyroid adenomas were demonstrated to be of monoclonal origin. Contrary to the traditional histological crieria, majority of the primary (2/2) and secondary multigland hyperplasia (19/27, 70.4%) were also of monoclonal origin. A progression from polyclonal hyperplasia to monoclonal neoplasia might be present in the development of SHPT.3. Different parath … More yroid disorders were related to different genetic abnormalities. 1). Not only in parathyroid carcinomas, but also in parathyroid adenomas, particularly those with nuclear pleomorphism, were detected overexpression of p53 protein (4/32), somatic mutation (R290H), polymorphism (L252L,R72P) and LOH.2). Abnormality of MEN 1 gene (W1 98X, A340T, A541T, T429K, D418D, V367V) was identified in both MEN 1 and sporadic endocrin tumors (parathyroid adenoma and pancreatic endocrine tumor), but only in less than 20% of parathyroid adenomas. 3). Different from MEN 1 gene, ret oncogene mutation seemed to be unrelated to parathyroid adenomas (0/16), although its somatic mutation was found in 32.5% (13/40) of thyroid medullary carcinoma. 4). In the parathyroids (20 glands) with SHPT, we have failed to find any abnormalities of p53, MEN 1 and 1 p35-36.Conclusion : 1. Parathyroid adenomas are of monoclonal origin, related to multiple genetic abnormalities. 2. Clonal analysis suggests a progression from polyclonal hyperplasia to monoclonal neoplasia in the SHPT with unknown genetic abnormality. 3. The distribution pattern of PTH hormone protein, clonality and genetic analysis are helpful in the differentiation between hyperplastic lesions and neoplasia. Less