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Stem Cell Transcription Factor Sox2 Is Expressed in a Subset of Folliculo-stellate Cells of Growth Hormone-Producing Pituitary Neuroendocrine Tumours and Its Expression Shows No Association with Tumour Size or IGF1 Levels: a Clinicopathological Study of 109 Cases.
Endocrine Pathology ( IF 4.4 ) Pub Date : 2020-07-06 , DOI: 10.1007/s12022-020-09634-1
Jiri Soukup 1 , Tomáš Česák 2 , Helena Hornychová 1 , Květoslava Michalová 3, 4 , Ľudmila Michnová 5 , David Netuka 6 , Jan Čáp 7 , Filip Gabalec 7
Affiliation  

Sox2 is one of the transcription factors responsible for the maintenance of stem cell phenotype. It has been implicated as a marker of stem cells in normal pituitaries and pituitary neuroendocrine tumours. To explore the clinical significance of Sox2 expression in histological sections, we performed immunohistochemical detection of Sox2 in 113 pituitary neuroendocrine tumours from 109 patients with acromegaly. In 11 tumours, we performed double immunostaining for Sox2, annexin A1 and S100 protein. Tumours were characterised using the WHO classification system. Proliferative activity and invasion were assessed. The amount of immunoreactive cells was evaluated and correlated with tumour size and biochemical features (levels of IGF1, GH, prolactin, βTSH). Sox2+ cells were identified in 35/38 normal pituitaries adjacent to the tumours. In 36 tumours (33%), ≥ 1% of the cells expressed Sox2, in 24 cases (22%), Sox2+ cells comprised < 1% and 49 cases (45%) were negative. We found no significant differences between Sox2+ and Sox2 groups with respect to the age, initial levels of GH, IGF1, prolactin, βTSH, tumour size, invasion, proliferative activity or histological features. We observed a positive correlation between Sox2+ cell count and βTSH immunoreactive cells (r = 0.459, p < 0.001) that was further verified by multivariate analysis. Using double stain, the majority of Sox2+ cells coexpressed annexin A1 (average 89%) and S100 protein (average 76.2%) and showed morphological features of folliculo-stellate cells. Sox2+ cells are thus commonly present in growth hormone–producing tumours and normal pituitaries, and their amount does not have any prognostic significance. Most of these cells represent a subpopulation of folliculo-stellate cells, pointing out to their role as a possible stem cell population.



中文翻译:

干细胞转录因子 Sox2 在产生生长激素的垂体神经内分泌肿瘤的毛囊星状细胞亚群中表达,其表达与肿瘤大小或 IGF1 水平无关:109 例临床病理学研究。

Sox2 是负责维持干细胞表型的转录因子之一。它被认为是正常垂体和垂体神经内分泌肿瘤中干细胞的标志物。为了探索组织切片中 Sox2 表达的临床意义,我们对 109 名肢端肥大症患者的 113 例垂体神经内分泌肿瘤中的 Sox2 进行了免疫组织化学检测。在 11 个肿瘤中,我们对 Sox2、膜联蛋白 A1 和 S100 蛋白进行了双重免疫染色。使用WHO分类系统表征肿瘤。评估增殖活性和侵袭。评估免疫反应细胞的数量并与肿瘤大小和生化特征(IGF1、GH、催乳素、βTSH 的水平)相关联。Sox2 +在与肿瘤相邻的 35/38 个正常垂体中鉴定出细胞。在 36 个肿瘤 (33%) 中,≥ 1% 的细胞表达 Sox2,在 24 个病例 (22%) 中,Sox2 +细胞组成 < 1%,49 个病例 (45%) 为阴性。我们发现 Sox2 +和 Sox2 -组在年龄、GH、IGF1、催乳素、βTSH、肿瘤大小、侵袭、增殖活性或组织学特征的初始水平方面没有显着差异。我们观察到 Sox2 +细胞计数和 βTSH 免疫反应细胞之间的正相关(r  = 0.459,p  < 0.001),这通过多变量分析进一步验证。使用双染色,大部分 Sox2 +细胞共表达膜联蛋白A1(平均89%)和S100蛋白(平均76.2%),表现出滤泡星状细胞的形态特征。Sox2 +细胞因此通常存在于产生生长激素的肿瘤和正常垂体中,它们的数量没有任何预后意义。大多数这些细胞代表毛囊星状细胞的一个亚群,指出它们作为可能的干细胞群的作用。

更新日期:2020-07-06
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