HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas

Abstract

Intrahepatic cholangiocarcinoma (iCCA) needs to be distinguished from hepatocellular carcinoma (HCC) and metastasis, and in the absence of any specific biliary markers, is often a diagnosis of exclusion. Hepatocyte nuclear factor (HNF)-1β is a transcription factor that plays a critical role in bile duct system morphogenesis. To investigate the diagnostic value of HNF-1β to differentiate iCCA from HCC by immunohistochemistry and compare HNF-1β with C-reactive protein (CRP), a previously identified marker for iCCA. Cases of iCCA (n = 75), combined hepatocellular-cholangiocarcinoma (cHCC-CCA) (n = 13) and HCC (n = 65) were included in the study. All cases of iCCA (74 of 74, 100%) expressed HNF-1β compared with CRP expressed in 72.60% (53 of 73). The sensitivity and specificity of HNF-1β to differentiate iCCA from HCC was 100% and 92.31%, whereas the sensitivity and specificity for CRP was 75.58% and 7.79%. The expression of HNF-1β was greater in iCCA and the CCA component of cHCC-CCA compared with CRP (87 of 87, 100% versus 65 of 86, 75.58%; P < .001). On the contrary, CRP was more frequently expressed compared with HNF-1β in HCC and HCC component of cHCC-CCA (71 of 77, 92.21% versus 6 of 78, 7.69%; P < .001). Our data indicate that HNF-1β is a more sensitive and specific marker than CRP for the diagnosis of iCCA and to identify the CCA component in cHCC-CCA. Lack of HNF-1β expression may be used to exclude iCCA from consideration in cases of adenocarcinomas of unknown primary.