The correlation between poor prognosis and increased yes-associated protein 1 expression in keratin 19 expressing hepatocellular carcinomas and cholangiocarcinomas

BMC Cancer

Research Article

KyuHo Lee¹  Kyoung-Bun Lee¹  Hae Yoen Jung¹  Ja-June Jang¹  Nam-Joon Yi²  Kyung-Suk Suh²  Kwang-Woong Lee² 

[1] Department of Pathology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, 110-744, Seoul, South Korea;Department of Surgery, Seoul National University College of Medicine, 110-744, Seoul, South Korea;

关键词: YAP1;    Hepatocellular carcinoma;    Cholangiocarcinoma;    Combined hepatocellular and cholangiocarcinoma;    Progenitor cell;   

DOI  :  10.1186/s12885-017-3431-1

 received in 2016-06-22, accepted in 2017-06-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe Hippo pathway plays a vital role in liver regeneration and development by determining cellular lineage and regulating cell proliferation and apoptosis. In this study, we aimed to assess the role of the Hippo pathway in hepatic carcinogenesis and morphogenesis by examining Yes-associated protein 1 (YAP1) expression in the spectrum of hepatic carcinomas based on cellular lineage.MethodsWe examined 913 primary hepatic carcinomas, including hepatocellular carcinomas (HCCs), combined hepatocellular and cholangiocarcinomas (cHC-CCAs), intrahepatic cholangiocarcinomas (IHCCAs) and perihilar extrahepatic bile duct carcinomas (EHBCAs). Our study group was categorized into 8 disease groups, based on histological diagnosis and cytokeratin 19 (CK19) expression, and immunohistochemistry was used to detect and compare YAP1 expression levels between the groups. The eight disease groups we identified were: 1) CK19(−) HCC, 2) CK19(−) scirrhous HCC, 3) CK19(+) HCC, 4) stem cell feature of cHC-CCA, 5) classical cHC-CCA, 6) cholangiolocellular IHCCA, 7) non-cholangiolocellular IHCCA, and 8) EHBCA.ResultsPositive rates of YAP1 were the highest in the EHBCA group (21%). CK19(+) HCC and non-cholangiolocellular IHCCA groups also showed high expression levels (10% -11%), while the CK19 (−) HCC, CK19 (−) scirrhous HCC, cHC-CCA, and cholangiolocellular IHCCA groups showed low expression levels, ranging between 0% and 5%. Survival analysis, restricted to pT1 stage HCCs and IHCCAs, showed poor overall survival for YAP1(+) IHCCA patients (39 ± 17 vs. 109 ± 10 months, mean ± SD, log rank p-value 0.005). For HCCs, a trend of poor progression-free survival for YAP1(+) HCCs was observed (39 ± 18 vs. 81 ± 5 months, mean ± SD, log rank p-value 0.205)ConclusionsYAP1 activation was more commonly found in CCAs than in pure HCCs. However, a differing pattern of YAP1 expression between cHC-CCAs and CK19(+) HCCs and the poor prognosis of YAP1 positive hepatic carcinomas suggests that YAP1 may have a preferential role in aggressive tumor behavior, rather than in the determination of cellular lineage in hepatic carcinomas.

【 授权许可】

CC BY   
© The Author(s). 2017