Expression of Hepatocyte and Cholangiocyte Transcription Factors in Hepatocellular Carcinoma, Cholangiocarcinoma, and Combined Hepatocellular and Cholangiocarcinoma: Implication for the Process of Transdifferentiation
E Sasatomi, E Ochoa, K Isse, MA Nalesnik, T Wu, AJ Demetris. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: Hepatocyte nuclear factors (HNFs) are a subfamily of transcription factors that are known to play important roles in the division of hepatocyte and biliary lineages in early liver development. The purpose of the study is to examine the expression status of different HNFs in hepatocellular carcinoma (HCC), peripheral intrahepatic cholangiocarcinoma (ICC), and in the different histologic components of combined hepatocellular and cholangiocarcinoma (HCC-CC).
Design: Five cases of ICC, 6 cases of HCC and 7 cases of HCC-CC were gathered from the pathology archives of the University of Pittsburgh Medical Center (UPMC). By definition, unequivocal component of hepatocellular carcinoma with trabecular or solid nests separated by sinusoidal spaces (hcc) and cholangiocarcinoma component with tubular glandular structures accompanied by fibrous stroma (cc) were observed within the same nodule in cases of HCC-CC. Areas of sarcomatoid differentiation (src) were seen in two cases (29%) of HCC-CC. Immunohistochemical stains for HNF1, HNF1, HNF4, and HNF6 were performed in all cases.
Results: HCC was characterized by negative expression for HNF1 and HNF1 (Table 1).
Table 1. Expression status of HNFs in ICC, HCC and HCC-CC
|HNF1||20% (1/5)||0% (0/6)||43% (3/7)|
|HNF1||100% (5/5)||0% (0/6)||57% (4/7)|
|HNF4||60% (3/5)||67% (4/6)||100% (7/7)|
|HNF6||40% (2/5)||17% (1/6)||71% (5/7)|
HNF1 was expressed exclusively in ICC or cc component of HCC-CC (Tables 1 and 2).
Table 2. Expression status of HNFs in different components of HCC-CC
|HNF1||43% (3/7)||14% (1/7)||0% (0/2)|
|HNF1||57% (4/7)||0% (0/7)||0% (0/2)|
|HNF4||71% (5/7)||86% (6/7)||50% (1/2)|
|HNF6||43% (3/7)||43% (3/7)||0% (0/2)|
HNF4 and HNF6 were observed both in HCC and CC and in hcc and cc components of HCC-CC. Sarcomatoid component of HCC-CC was positive only for HNF4.
Conclusions: Because HNF1 was observed exclusively in the areas of cholangiocellular differentiation, HNF1 may play a role in the pathogenesis of cholangiocarcinoma. Immunostain for HNF1 may serve as a marker for biliary epithelial differentiation in the diagnosis of liver neoplasm.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 175, Tuesday Morning