肝细胞核因子(HNF)6和4α是小鼠和人类肝脏和胰胆管发育和维持的主要转录调节因子。然而,关于HNF6和HNF4α表达在肝胆道和胰腺癌中的患病率知之甚少。我们旨在揭示HNF6和HNF4α免疫标记在这些器官的腺癌中的诊断效用。我们使用总共480个消化系统腺癌,通过免疫组织化学研究了HNF6和HNF4α的表达,包括282个肝胆道和胰腺和198个胃肠道。HNF6表达主要限于肝内胆管癌(CCs)(63%,n=80)和胆囊腺癌(43%,n=88),在其他人中。值得注意的是,小导管肝内CCs几乎总是表达HNF6(90%,n=42),与大导管肝内CC的低患病率形成鲜明对比(10%,n=21;p<0.0001)。HNF6在肝外CCs中表达很少(9%,n=55)和胰腺导管腺癌(7%,n=58),在胃肠道腺癌[食管/食管胃结合部(EGJ)(2%,n=45),胃(2%,n=86),十二指肠(0%,n=25),和结肠直肠(0%,n=42)]。相比之下,HNF4α在消化系统腺癌中广泛表达,包括肝内CCs(88%),肝外CCs(94%),胆囊腺癌(98%),胰腺(98%),食管/EGJ(96%),胃(98%),十二指肠(80%),和结肠直肠(100%)。HNF6经常在小导管型和胆囊腺癌的肝内CCs中表达并几乎限于此。而HNF4α在整个消化系统腺癌中表达。HNF6免疫标记可用于区分小导管肝内CC与其他类型的CC以及转移性胃肠道腺癌。
Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and humans. However, little is known about the prevalence of HNF6 and HNF4α expression in carcinomas of the hepatobiliary tract and pancreas. We aimed to reveal the diagnostic utility of HNF6 and HNF4α immunolabelling in adenocarcinomas of these organs. We investigated HNF6 and HNF4α expression by immunohistochemistry using a total of 480 adenocarcinomas of the digestive system, including 282 of the hepatobiliary tract and pancreas and 198 of the gastrointestinal tract. HNF6 expression was primarily restricted to intrahepatic cholangiocarcinomas (CCs) (63%, n=80) and gallbladder adenocarcinomas (43%, n=88), among others. Notably, small duct intrahepatic CCs almost invariably expressed HNF6 (90%, n=42), showing stark contrast to a low prevalence in large duct intrahepatic CCs (10%, n=21; p<0.0001). HNF6 expression was infrequent in extrahepatic CCs (9%, n=55) and pancreatic ductal adenocarcinomas (7%, n=58), and it was rare in adenocarcinomas of the gastrointestinal tract [oesophagus/oesophagogastric junction (EGJ) (2%, n=45), stomach (2%, n=86), duodenum (0%, n=25), and colorectum (0%, n=42)]. In contrast, HNF4α was widely expressed among adenocarcinomas of the digestive system, including intrahepatic CCs (88%), extrahepatic CCs (94%), adenocarcinomas of the gallbladder (98%), pancreas (98%), oesophagus/EGJ (96%), stomach (98%), duodenum (80%), and colorectum (100%). HNF6 was frequently expressed in and almost restricted to intrahepatic CCs of small duct type and gallbladder adenocarcinomas, while HNF4α was expressed throughout adenocarcinomas of the digestive system. HNF6 immunolabelling may be useful in distinguishing small duct intrahepatic CCs from other types of CC as well as metastatic gastrointestinal adenocarcinomas.