Objectives

Thymic epithelial tumors are the most common adult mediastinal tumors; however, their growth mechanism remains relatively unknown. Among the JAK/STAT pathway-related proteins, which control various intracellular events, STAT3 is deeply involved in cell proliferation. Constitutive activation of STAT3 and the resulting overexpression of cyclin D1 have been confirmed in various tumors, but have not been thoroughly investigated in thymic epithelial tumors. In this study, we immunohistochemically examined STAT3 activation, cyclin D1 expression, and JAK3 activation in thymic epithelial tumors and statistically analyzed their correlation with clinicopathological features.

Methods

Formalin-fixed paraffin-embedded specimens of 94 thymic epithelial tumors surgically resected at Kyorin University Hospital between 2005 and 2018 were included in this study. pSTAT3, cyclin D1, and pJAK3 were immunohistochemically examined, and the correlation with histology, Masaoka stage, and survival time was statistically analyzed.

Results

Cyclin D1 was found to be significantly overexpressed in the STAT3-activated group. This phenomenon was associated with histology and Masaoka stage. JAK3 was also activated in thymic epithelial tumors; however, JAK3 and STAT3 activation were not always correlated. Using survival time analysis, the STAT3-activated group, cyclin D1-expressed group, and JAK3-activated group had significantly lower progression-free survival times than those for both the non-activated and non-expressed groups.

Conclusions

STAT3 activation may promote cyclin D1 overexpression in thymic epithelial tumors, and intracellular signaling pathways other than JAK3 may be involved in STAT3 activation. STAT3 activation, cyclin D1 overexpression, and JAK3 activation are biomarker candidates that indicate clinically poor prognosis.

中文翻译：

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胸腺上皮肿瘤中 STAT3 的激活：与细胞周期蛋白 D1、JAK3 和临床行为的相关性

目标

胸腺上皮肿瘤是最常见的成人纵隔肿瘤；然而，它们的生长机制仍然相对未知。在控制各种细胞内事件的 JAK/STAT 通路相关蛋白中，STAT3 与细胞增殖密切相关。STAT3 的组成型激活和由此产生的细胞周期蛋白 D1 的过表达已在各种肿瘤中得到证实，但尚未在胸腺上皮肿瘤中进行彻底研究。在这项研究中，我们对胸腺上皮肿瘤中的 STAT3 激活、细胞周期蛋白 D1 表达和 JAK3 激活进行了免疫组织化学检测，并统计分析了它们与临床病理学特征的相关性。

方法

本研究纳入了 2005 年至 2018 年间在 Kyorin 大学医院手术切除的 94 例胸腺上皮肿瘤的福尔马林固定石蜡包埋标本。对pSTAT3、cyclin D1、pJAK3进行免疫组化检测，统计分析与组织学、正冈分期、生存时间的相关性。

结果

发现 Cyclin D1 在 STAT3 激活组中显着过表达。这种现象与组织学和正冈分期有关。JAK3 在胸腺上皮肿瘤中也被激活；然而，JAK3 和 STAT3 的激活并不总是相关的。使用生存时间分析，STAT3 激活组、cyclin D1 表达组和 JAK3 激活组的无进展生存时间显着低于非激活组和非表达组。

结论

STAT3 激活可能促进胸腺上皮肿瘤中 cyclin D1 过表达，除 JAK3 外的细胞内信号通路可能参与 STAT3 激活。STAT3 激活、细胞周期蛋白 D1 过表达和 JAK3 激活是表明临床预后不良的候选生物标志物。