Krohn Knut, Stricker Ingo, Emmrich Peter, Paschke Ralf
III Medical Department, and Interdisciplinary Centre for Clinical Research, University of Leipzig, Leipzig, Germany.
Thyroid. 2003 Jun;13(6):569-75. doi: 10.1089/105072503322238836.
Thyroid follicular adenomas and adenomatous thyroid nodules are a frequent finding in geographical areas with iodine deficiency. They occur as hypofunctioning (scintigraphically cold) or hyperfunctioning (scintigraphically hot) nodules. Their predominant clonal origin suggests that they result from clonal expansion of a single cell, which is very likely the result of a prolonged increase in proliferation compared with non-affected surrounding cells. To test whether increased cell proliferation is detectable in cold thyroid nodules, we studied paraffin-embedded tissue from 40 cold thyroid nodules and their surrounding normal thyroid tissue for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) epitopes as markers for cell proliferation. All 40 thyroid nodules were histologically well characterized and have been studied for molecular characteristics before. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. In 33 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for PCNA was detectable. In 19 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for Ki-67 was detectable. Moreover, surrounding tissues with lymphocyte infiltration showed a significantly higher labeling index for both PCNA and Ki-67 compared with normal surrounding tissue. These findings are first evidence that an increased thyroid epithelial cell proliferation is a uniform feature common to most cold nodules. However, the increase of proliferation markers shows a heterogeneity that is not correlated with histopathologic, molecular, or clinical characteristics.
甲状腺滤泡性腺瘤和甲状腺腺瘤性结节在碘缺乏地区很常见。它们表现为功能减退（放射性核素扫描显示为冷结节）或功能亢进（放射性核素扫描显示为热结节）的结节。其主要的克隆起源表明它们是由单个细胞的克隆性扩增导致的，这很可能是与未受影响的周围细胞相比增殖持续增加的结果。为了检测在冷甲状腺结节中是否可检测到细胞增殖增加，我们研究了40个冷甲状腺结节及其周围正常甲状腺组织的石蜡包埋组织，以检测增殖细胞核抗原（PCNA）和Ki-67（MIB-1抗体）表位作为细胞增殖的标志物。所有40个甲状腺结节在组织学上均有明确特征，并且之前已对其分子特征进行过研究。计算结节和周围组织的标记指数（标记细胞数与总细胞数之比）。在33个冷甲状腺结节中可检测到PCNA标记指数显著（p≤0.05）增加。在19个冷甲状腺结节中可检测到Ki-67标记指数显著（p≤0.05）增加。此外，与正常周围组织相比，有淋巴细胞浸润的周围组织PCNA和Ki-67的标记指数均显著更高。这些发现首次证明甲状腺上皮细胞增殖增加是大多数冷结节共有的一个一致特征。然而，增殖标志物的增加表现出异质性，且与组织病理学、分子或临床特征无关。
