First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Department of Pathology, Paracelsus Medical University, 90419 Nuremberg, Germany.
Int J Mol Sci. 2022 Jul 28;23(15):8339. doi: 10.3390/ijms23158339.
Background: Recent advances demonstrate the role of chromatin regulators, including histone variants and histone chaperones, in cancer initiation and progression. Methods: Histone H3K4me3, histone variant centromere protein (CENP-A) and histone chaperones Holliday junction recognition protein (HJURP) as well as DAXX expression were examined immunohistochemically in 95 thymic epithelial tumor (TET) specimens. Our results were compared with the expression profile of DAXX, HJURP and CENP-A in gene expression profiling interactive analysis (GEPIA2). Results: The lymphocyte-poor B3- and C-type TETs were more frequently DAXX negative (p = 0.043). B3 and C-Type TETs showed higher cytoplasmic and nuclear CENP-A (p = 0.007 and p = 0.002) and higher cytoplasmic HJURP H-score (p < 0.001). Higher nuclear CENP-A and cytoplasmic HJURP expression was associated with advanced Masaoka−Koga stage (p = 0.048 and p < 0.001). A positive correlation between HJURP and CENP-A was also observed. The presence of cytoplasmic CENP-A expression was correlated with a favorable overall survival (p = 0.03). CENP-A overexpression in survival analysis of TCGA TETs showed similar results. H3K4me3 expression was not associated with any clinicopathological parameters. Conclusions: Our results suggest a significant interaction between CENP-A and HJURP in TETs. Moreover, we confirmed the presence of a cytoplasmic CENP-A immunolocalization, suggesting also a possible favorable prognostic value of this specific immunostaining pattern.
最近的进展表明,染色质调节因子,包括组蛋白变体和组蛋白伴侣,在癌症的发生和发展中起作用。方法:我们用免疫组化方法检测了 95 例胸腺瘤(TET)标本中的组蛋白 H3K4me3、组蛋白变体着丝粒蛋白(CENP-A)和组蛋白伴侣 Holliday 连接识别蛋白(HJURP)以及 DAXX 的表达情况。我们的结果与基因表达谱交互分析(GEPIA2)中 DAXX、HJURP 和 CENP-A 的表达谱进行了比较。结果:低淋巴细胞的 B3 型和 C 型 TET 中 DAXX 表达缺失的频率更高(p = 0.043)。B3 型和 C 型 TET 中,细胞质和核内 CENP-A 的表达更高(p = 0.007 和 p = 0.002),细胞质中 HJURP 的 H 评分更高(p < 0.001)。核内 CENP-A 和细胞质 HJURP 的表达与较高的 Masaoka-Koga 分期相关(p = 0.048 和 p < 0.001)。此外,还观察到 HJURP 与 CENP-A 之间存在正相关关系。细胞质中 CENP-A 的表达与总生存率呈正相关(p = 0.03)。TCGA TETs 中 CENP-A 过表达的生存分析也得出了类似的结果。H3K4me3 的表达与任何临床病理参数均无相关性。结论:我们的结果表明,在 TET 中 CENP-A 与 HJURP 之间存在显著的相互作用。此外,我们还证实了细胞质中 CENP-A 的免疫定位,这也提示了这种特定免疫染色模式可能具有良好的预后价值。