论文标题：Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma (上尿路尿路上皮癌中GATA3和错配修复蛋白的表达情况)

期刊：

作者：Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He

发表时间：22 Apr 2019

DOI：10.1007/s11684-019-0687-7

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导读 北京大学首钢医院病理科王跃和北京大学明升手机版部病理系贺慧颖等在Frontiers of Medicine 发表论文《上尿路尿路上皮癌中GATA3和错配修复蛋白的表达情况》（）。

GATA3和微卫星不稳定分别被证实在尿路上皮癌的发展中具有重要作用。研究报道GATA3通过阻断TGF-β信号通路抑制乳腺癌转移；微卫星不稳定与结直肠癌TGF-β受体高频失活突变密切相关。本研究旨在探讨GATA3和MSI在上尿路尿路上皮癌中的表达及临床病理意义。

摘 要 GATA3和MSI分别被证实在尿路上皮癌的发展中具有重要作用，然而尚未有报道两者共同表达情况及预后意义。本研究发现GATA3与预后不良指标（分期、脉管内瘤栓、神经侵犯、淋巴结转移、大片坏死）显著负相关，与肿瘤特异性生存期和无病生存期显著正相关。本研究中MMR在8.3%病例中阴性表达，13.0%小灶阳性（< 5%）。 GATA3表达与MSI负性相关。与GATA3+/MSI 病例相比，GATA3-/ MS患者分期更晚、预后更差。此外，GATA3-/MSI患者比GATA3+/MSI患者预后差。GATA3是否通过TGF-β信号通路与MSI相互作用，以及如何调控上尿路尿路上皮癌的进展有待进一步研究。

摘要

GATA binding protein 3 (GATA3) and mismatch repair (MMR) deficiency contribute to the development of urothelial carcinoma. However, the combined expression of GATA3 and microsatellite instability (MSI) in upper tract urothelial carcinoma (UTUC) and its prognostic value have not been investigated. Here, we immunohistochemically stained GATA3 and MMR proteins in 108 UTUC samples. GATA3 was positive in 74 cases, and its expression was significantly lower than in adjacent benign urothelium (P<0.001). Loss of GATA3 expression was statistically associated with adverse clinicopathologic parameters, such as advanced stage, lymphovascular invasion, neural invasion, lymph node metastasis, and extensive necrosis. Cancer-specific survival (CSS, P=0.028) and disease-free survival (DFS, P=0.024) were significantly shorter in patients with GATA3 negative tumors than in patients with GATA3 positive tumors. The absence of MMR proteins was observed in 8.3% of the cases, and focal staining was identified in 13.0%. When using “lax criteria” which resulted in counting cases as negative where MMR staining was in fact focally positive (<5%), we found that GATA3 was inversely associated with MSI (P=0.005). Moreover, GATA3−/microsatellite stability (MS) tumors were correlated with advanced pT stage (P<0.001) and poor outcome (P=0.019 for CSS, P=0.016 for DFS) compared with GATA3+/MSI ones. The GATA3−/MSI cases had unfavorable clinical outcomes compared with GATA3+/MSI cases (P=0.008 for CSS, P=0.023 for DFS). This finding raises a question as to whether GATA3 interacts with MSI through the TGF-β signaling pathway and regulates UTUC progression.

原文信息

标题

Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma

作者

Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He

机构

1. Department of Pathology, Peking University Shougang Hospital, Beijing 100144, China

2. Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100083, China

Corresponding Author Huiying He

Cite this article

Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He. Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma. Front. Med., 2019, 13(6): 730?740

微信号：frontmed

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