The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease.
The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease.
复制标题
DOI：
10.1016/j.humpath.2014.01.002
复制
发表时间：
2014-05
期刊：
影响因子：
3.3
通讯作者：
Anders, Robert A.
中科院分区：
文献类型：
--
作者：
Gurda, Grzegorz T.;Zhu, Qingfeng;Bai, Haibo;Pan, Duojia;Schwarz, Kathleen B.;Anders, Robert A.
关键词：
虽然新生儿生理性黄疸是常见的，但持续性的新生儿胆汁淤积是危及生命的，并且有多种病因。在这些病因中，胆道闭锁(BA)需要快速诊断和治疗。在诊断BA时，外科病理学家必须认识到细微的组织学变化，通常只进行一次小的核心肝脏活检。为了帮助鉴别诊断新生儿胆汁淤积症，我们研究了YAP，一种调节器官大小和胆管发育的蛋白。我们研究了YAP免疫染色是否可以与其他原因的持续性胆汁淤积(非BA)[n=15]相比，突出BA[n=28]中出现的肝胆上皮，从而作为新生儿持续性黄疸的有用诊断标记物。与非BA组相比，BA组的高级别(≤-2)纤维化和导管增生明显增多(p<0.01)。同样，BA(97%和%)的高级别(2-3/3)胞浆和胞核YAP染色显著高于非BA(20%和13%)。高级别细胞核YAP染色对BA诊断的敏感性(88%)和特异性(87%)。与新生儿胆汁淤积症相比，YAP在胆汁淤积/梗阻与非梗阻成人肝脏中的定位差异不显著。最后，我们发现，对胆管细胞和胆管癌细胞系中YAP复合体的药物抑制以时间和剂量依赖的方式阻断了胆管的代偿性增殖，这是BA的早期标志，需要核YAP的表达。综上所述，我们发现YAP的表达调节了胆管的增殖和肝脏的损伤/纤维化，同时作为鉴别诊断持续性新生儿胆汁淤积的敏感和特异的标记物。
Although physiologic jaundice of neonates is common, persistent neonatal cholestasis is life-threatening and has multiple etiologies. Among these etiologies, biliary atresia (BA) requires rapid diagnosis and treatment. In diagnosing BA, the surgical pathologist must recognize subtle histologic changes, often with only a small core liver biopsy. To aid in the differential diagnosis of neonatal cholestasis, we investigated Yes-associated protein (YAP), a regulator of organ size and bile duct development. We examined whether a YAP immunostain can highlight emerging hepatobiliary epithelium in BA [n=28] versus other causes of persistent cholestasis (non-BA) [n=15] and thus serve as a useful diagnostic marker in persistent neonatal jaundice. We show significantly (p≤0.01) more high-grade (≤2) fibrosis and ductular proliferation among BA versus non-BA cases. Likewise, there was significantly more high-grade (2–3/3) cytoplasmic and nuclear YAP staining in BA (97% and 89%) versus non-BA (20% and 13%). High-grade nuclear YAP staining was both sensitive (88%) and specific (87%) for the diagnosis of BA. In contrast to neonatal cholestasis, the differences in YAP localization in cholestatic/obstructed vs. non-obstructed adult livers were not significant. Lastly, we found that pharmacological inhibition of the YAP complex in both cholangiocyte and cholangiocarcinoma cell lines blocked compensatory bile duct proliferation, an early marker of BA that requires nuclear YAP expression, in a time- and dose-dependent manner. In summary, we show that YAP expression modulates both bile duct proliferation and liver damage/fibrosis while acting as a sensitive and specific marker in the differential diagnosis of persistent neonatal cholestasis.
登录
查看更多内容
影响因子：
7.3
作者：
Mehlen, Patrick
通讯作者：
Mehlen, Patrick
影响因子：
12.6
作者：
Russo, Pierre;Magee, John C.;Boitnott, John;Bove, Kevin E.;Raghunathan, Trivellore;Finegold, Milton;Haas, Joel;Jaffe, Ronald;Kim, Grace E.;Magid, Margret;Melin-Aldana, Hector;White, Frances;Whitington, Peter F.;Sokol, Ronald J.
通讯作者：
Sokol, Ronald J.
DOI：
10.1038/modpathol.2011.212
发表时间：
2012-05
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.4
作者：
Davenport, M;Gonde, C;Howard, ER
通讯作者：
Howard, ER
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia