Preto Ana, Cameselle-Teijeiro José, Moldes-Boullosa Julio, Soares Paula, Cameselle-Teijeiro Jorge F, Silva Paula, Reis-Filho Jorge S, Reyes-Santías Rosa M, Alfonsín-Barreiro Natividad, Forteza Jerónimo, Sobrinho-Simões Manuel
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
Mod Pathol. 2004 Jul;17(7):819-26. doi: 10.1038/modpathol.3800124.
Solid cell nests of the human thyroid gland are composed of main cells and C cells. In order to investigate the putative stem cell nature of the role for solid cell nests, we evaluated the histological features, and the immunohistochemical expression of p63, bcl-2, telomerase catalytic subunit, and two proliferative markers (Ki-67 and minichromosome maintenance protein 2), in a series of 24 cases of solid cell nests. Proliferative indices were determined in (a) solid cell nests, (b) thyroid follicular cells in the vicinity of solid cell nests within a low-power field, and (c) distant thyroid tissue, at a distance of at least three low-power fields from solid cell nests. In 15 cases of solid cell nests (62.5%), mixed follicles were observed; papillary formations were observed in four cases (16.6%), and ciliated cells were observed in the lining of microcysts associated with two cases (8.3%). Salivary gland-type tissue, cartilage islands, adipose and fibrous tissues, and small nerves were also associated with some cases of solid cell nests. We observed that the main cells of the solid cell nests express consistently telomerase, although at lower levels than p63, and show strong cytoplasmic immunoreactivity for bcl-2, which is associated with an increased differentiation potential. We also observed that despite their relative low proliferative index, main cells of the solid cell nests display higher proliferation than follicular cells in the vicinity and follicular cells in more distant thyroid tissue. We conclude that main cells of the solid cell nests apparently harbor the minimal properties of a stem cell phenotype (capacity for both self-renewal, conferred by telomerase activity, and differentiation to one or more than one type of specialized cells, given by the high expression of p63 and bcl-2) and may thus represent a pool of stem cells of the adult thyroid.
人类甲状腺的实性细胞巢由主细胞和C细胞组成。为了研究实性细胞巢的假定干细胞特性及其作用,我们评估了24例实性细胞巢的组织学特征,以及p63、bcl-2、端粒酶催化亚基和两种增殖标志物(Ki-67和微小染色体维持蛋白2)的免疫组化表达。增殖指数在以下部位测定:(a)实性细胞巢;(b)低倍视野下实性细胞巢附近的甲状腺滤泡细胞;(c)距实性细胞巢至少三个低倍视野的远处甲状腺组织。在15例实性细胞巢(62.5%)中观察到混合滤泡;在四例(16.6%)中观察到乳头形成,在两例(8.3%)伴有微囊肿的衬里中观察到纤毛细胞。涎腺型组织、软骨岛、脂肪和纤维组织以及小神经也与一些实性细胞巢病例相关。我们观察到实性细胞巢的主细胞持续表达端粒酶,尽管水平低于p63,并对bcl-2显示出强烈的细胞质免疫反应性,这与分化潜能增加有关。我们还观察到,尽管实性细胞巢的主细胞增殖指数相对较低,但与附近的滤泡细胞和更远处甲状腺组织中的滤泡细胞相比,其增殖程度更高。我们得出结论,实性细胞巢的主细胞显然具有干细胞表型的最小特性(通过端粒酶活性赋予自我更新能力,以及通过p63和bcl-2的高表达赋予向一种或多种类型的特化细胞分化的能力),因此可能代表成人甲状腺的干细胞池。