背景:乳腺叶状肿瘤(PT)是不常见的纤维上皮肿瘤,倾向于局部复发并可能具有转移潜力。他们的发病机制知之甚少。Hippo信号通路在器官大小控制中起着至关重要的作用,肿瘤抑制,组织再生和干细胞自我更新。Hippo信号传导功能障碍与癌症有关。最近的证据表明,Hippo信号传导关键蛋白YAP/TAZ与上皮-间质转化(EMT)主调节因子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PT中的表达。与肿瘤分级有关。
方法:Hippo信号效应蛋白YAP的表达,通过免疫组织化学在86例人叶状乳腺肿瘤的石蜡包埋组织标本中评估了TAZ及其DNA结合伴侣TEAD(45例良性,21边界线,20恶性),与肿瘤分级以及EMT相关转录因子ZEB和Snail的表达相比。
结果:YAP的核免疫阳性,在PT的基质和上皮细胞中均检测到TAZ和TEAD,并且在高级别肿瘤中明显更高。有趣的是,YAP的表达之间存在显著的相关性,TAZ,TEAD与ZEB和SNAIL的表达有关。
结论:我们的结果最初暗示Hippo信号通路在PT发病机制中,并提示Hippo信号传导关键成分与EMT调节因子之间的相互作用可能促进PT的恶性特征。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.