Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Rion, Greece; Department of Surgery, University Hospital of Patras, Rion, Greece.
Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Rion, Greece.
Pathol Res Pract. 2024 Oct;262:155551. doi: 10.1016/j.prp.2024.155551. Epub 2024 Aug 15.
Phyllodes tumors (PTs) of the breast are uncommon fibroepithelial neoplasms that tend to recur locally and may have metastatic potential. Their pathogenesis is poorly understood. Hippo signaling pathway plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. Hippo signaling dysfunction has been implicated in cancer. Recent evidence suggests that there is cross-talk between the Hippo signaling key proteins YAP/TAZ and the epithelial-mesenchymal transition (EMT) master regulators Snail and ZEB. In this study we aimed to investigate the expression of Hippo signaling pathway components and EMT regulators in PTs, in relation to tumor grade.
Expression of Hippo signaling effector proteins YAP, TAZ and their DNA binding partner TEAD was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 86 human phyllodes breast tumors (45 benign, 21 borderline, 20 malignant), in comparison with tumor grade and with the expression of EMT-related transcription factors ZEB and Snail.
Nuclear immunopositivity for YAP, TAZ and TEAD was detected in both stromal and epithelial cells in PTs and was significantly higher in high grade tumors. Interestingly, there was a significant correlation between the expression of YAP, TAZ, TEAD and the expression of ZEB and SNAIL.
Our results originally implicate Hippo signaling pathway in PTs pathogenesis and suggest that an interaction between Hippo signaling key components and EMT regulators may promote the malignant features of PTs.
乳腺叶状肿瘤（PTs）是一种不常见的纤维上皮性肿瘤，往往容易局部复发，并且可能具有转移潜能。其发病机制尚不清楚。Hippo 信号通路在器官大小控制、肿瘤抑制、组织再生和干细胞自我更新中起着至关重要的作用。Hippo 信号通路功能障碍与癌症有关。最近的证据表明，Hippo 信号通路关键蛋白 YAP/TAZ 与上皮-间质转化（EMT）的主调控因子 Snail 和 ZEB 之间存在串扰。在这项研究中，我们旨在研究 Hippo 信号通路成分和 EMT 调节因子在叶状乳腺肿瘤中的表达，与肿瘤分级相关。
通过免疫组织化学方法评估 Hippo 信号效应蛋白 YAP、TAZ 及其 DNA 结合伴侣 TEAD 在 86 例人叶状乳腺肿瘤（45 例良性、21 例交界性、20 例恶性）石蜡包埋组织标本中的表达情况，与肿瘤分级以及 EMT 相关转录因子 ZEB 和 Snail 的表达进行比较。
在叶状肿瘤中，YAP、TAZ 和 TEAD 的核免疫阳性在间质和上皮细胞中均有检测到，在高级别肿瘤中更为显著。有趣的是，YAP、TAZ、TEAD 的表达与 ZEB 和 SNAIL 的表达之间存在显著相关性。
我们的研究结果最初提示 Hippo 信号通路参与了叶状肿瘤的发病机制，并表明 Hippo 信号关键成分与 EMT 调节因子之间的相互作用可能促进了叶状肿瘤的恶性特征。
