Velázquez-Fernández David, Laurell Cecilia, Saqui-Salces Milena, Pantoja Juan Pablo, Candanedo-Gonzalez Fernando, Reza-Albarrán Alfredo, Gamboa-Dominguez Armando, Herrera Miguel F
Department of Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Vasco de Quiroga 15, Tlalpan, 14000, Mexico D.F., Mexico.
World J Surg. 2006 May;30(5):705-13. doi: 10.1007/s00268-005-0708-3.
Differential diagnosis between adenoma and hyperplasia in primary hyperparathyroidism (pHPT) remains a dilemma. The aim of this study was to assess differences in transcriptional genomic expression profiles between sporadic (nonfamilial) parathyroid hyperplasia (SPH), adenoma, and normal tissue.
Parathyroid tissue from 12 patients with parathyroid adenoma, 3 with SPH, and 2 with normal glands was selected for analysis. Histopathology was reviewed in all cases, and all patients with adenomas presented normocalcemia for a minimum of 6 months after one gland resection. Hybridizations were performed in a microarray containing 19,968 human cDNA clones including contiguous replicates. Direct comparisons were performed with reverse labeling for every different pooled sample entity. Expression levels were analyzed using the SAM, SMA, LIMMA, Cluster, and PAM packages in the R environment for statistical computing.
There were significant statistical differences between SPH and adenomas. In the direct comparison, a total of 200 genes showed differential expression (P < 0.03): 61 genes were upregulated (> 1.65-fold increase) and 139 were downregulated (> 1.58-fold decrease) with a B value > 4.68 (99.08% probability of real differential expression). When SPH was compared to normal parathyroid tissue, 50 genes were differentially expressed: 42 were upregulated (> 1.89) and 8 were downregulated (> 1.7) with a B > 4.26 (98.6% probability of real differential expression). At least 17 genes were differentially expressed and able to discriminate SPH from adenoma or normal tissue. Upregulated genes were related to apoptosis inhibition, cell proliferation, transcriptional activity and cell adhesion, among other activities. Downregulated genes were mainly related to ion channel activity, lipopolysaccharides, prostaglandin-d synthase, and integral membrane proteins.
Our data suggest that SPH and adenoma have a singular molecular signature that, theoretically, could be used for the differential diagnosis of these entities and normal parathyroid tissue.
原发性甲状旁腺功能亢进症（pHPT）中腺瘤与增生的鉴别诊断仍然是一个难题。本研究的目的是评估散发性（非家族性）甲状旁腺增生（SPH）、腺瘤和正常组织之间转录基因组表达谱的差异。
选取12例甲状旁腺腺瘤患者、3例SPH患者和2例正常甲状旁腺组织患者的甲状旁腺组织进行分析。所有病例均进行了组织病理学检查，所有腺瘤患者在切除一个腺体后至少6个月血钙正常。在包含19,968个人类cDNA克隆（包括连续重复）的微阵列中进行杂交。对每个不同的混合样本实体进行反向标记直接比较。使用R环境中的SAM、SMA、LIMMA、Cluster和PAM软件包分析表达水平以进行统计计算。
SPH与腺瘤之间存在显著的统计学差异。在直接比较中，共有200个基因显示差异表达（P < 0.03）：61个基因上调（增加> 1.65倍），139个基因下调（降低> 1.58倍），B值> 4.68（真实差异表达概率为99.08%）。当将SPH与正常甲状旁腺组织进行比较时，50个基因差异表达：42个基因上调（> 1.89），8个基因下调（> 1.7），B > 4.26（真实差异表达概率为98.6%）。至少17个基因差异表达，能够区分SPH与腺瘤或正常组织。上调的基因与细胞凋亡抑制、细胞增殖、转录活性和细胞黏附等活动有关。下调的基因主要与离子通道活性、脂多糖、前列腺素 - d合成酶和整合膜蛋白有关。
我们的数据表明，SPH和腺瘤具有独特的分子特征，理论上可用于这些实体与正常甲状旁腺组织的鉴别诊断。
