Harrer P, Broecker M, Zint A, Schatz H, Zumtobel V, Derwahl M
Department of Surgery St. Josef-Hospital, Ruhr University of Bochum, Germany.
J Endocrinol Invest. 1998 Jun;21(6):380-5. doi: 10.1007/BF03350774.
Not only thyroid adenomas and carcinomas, but also the majority of single and well delimited goiter nodules, even if morphologically heterogeneous, are of clonal origin. However, it is still unknown whether the nodules of rapidly growing, recurrent goiters are clonal or polyclonal. We investigated by PCR-based analysis of exon 1 of the human androgen receptor gene clonality of nodules grown in recurrent multinodular goiters (MNG) of 14 female patients. The total goiter volume varied widely between 15 ml and 170 ml. The mean age of patients undergoing surgery for recurrent goiter at the time of their first operation was significantly lower with 34.6 +/- 10.9 yr in comparison to 50 consecutive patients who were operated for MNG for the first time (53.7 +/- 13.5 yr). The interval between first and recurrent operation was 18 +/- 8.5 yr. The mean volume of well circumscribed nodules selected for the present investigation was 3.8 +/- 1.4 ml. Assessment of clonality in at least 2 samples of each lesion revealed a polyclonal pattern in 10 out of 14 nodules, whereas only 3 nodules were clonal and in one case the result remained unclear. The unexpected finding that most nodules within MNG, that had re-grown after a first subtotal thyroidectomy, were of polyclonal rather than clonal composition, suggests that these lesions are generated by de novo-proliferation of cohorts of differing thyrocytes sharing the common trait of an exceedingly high intrinsic growth rate or alternatively, by unknown growth stimulating molecular events acting focally on clusters of cells derived from different ancestors. In addition, the relatively young age of patients with recurrent MNG at the time of their first surgery and the comparatively short interval between first and second operation point to a genetic element in the occurrence of growth-prone thyrocytes.
不仅甲状腺腺瘤和癌，而且大多数单个且边界清晰的甲状腺肿结节，即便形态上存在异质性，也都起源于克隆。然而，快速生长的复发性甲状腺肿结节是克隆性还是多克隆性仍不清楚。我们通过基于聚合酶链反应（PCR）的人雄激素受体基因外显子1分析，研究了14名女性患者复发性多结节性甲状腺肿（MNG）中生长的结节的克隆性。甲状腺肿总体积在15毫升至170毫升之间差异很大。首次手术时接受复发性甲状腺肿手术的患者的平均年龄显著更低，为34.6±10.9岁，相比之下，50名首次接受MNG手术的连续患者的平均年龄为53.7±13.5岁。首次手术和复发性手术之间的间隔为18±8.5年。本研究中选取的边界清晰的结节的平均体积为3.8±1.4毫升。对每个病变的至少2个样本进行克隆性评估发现，14个结节中有10个呈现多克隆模式，而只有3个结节是克隆性的，还有1例结果仍不明确。一个意外的发现是，大多数在首次甲状腺次全切除术后重新生长的MNG内的结节是多克隆而非克隆组成，这表明这些病变是由具有极高内在生长率这一共同特征的不同甲状腺细胞群体的从头增殖产生的，或者是由未知的生长刺激分子事件局部作用于来自不同祖先的细胞簇导致的。此外，复发性MNG患者首次手术时相对年轻的年龄以及首次和第二次手术之间相对较短的间隔表明，在易生长的甲状腺细胞的发生中存在遗传因素。
