Abstract
BackgroundCombined hepatocellular and cholangiocarcinoma (CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC); however, its cellular origin remains unclear. The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC.MethodsThe clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC (SHC). Loss of heterozygosity (LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC. Expression of hepatocyte markers [hepatocyte paraffin 1 (Hep Par 1) and glypican 3 (GPC3)] and cholangiocyte markers [cytokeratin (CK)7 and 19] in tumor tissues was examined by immuno histochemical analysis.ResultsIn the 16 CHC specimens, the difference in LOH patterns between HCC and ICC was less than 30%, suggesting the same clonal origin of HCC and ICC. Consistent with this finding, immunohistochemical analysis revealed that hepatocyte markers (Hep Par 1 and GPC3) and cholangiocyte markers (CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9% of CHC specimens, suggesting that the two components shared a similar phenotype with hepatic progenitor cells (HPCs). On the contrary, in all 10 SHC cases, the difference in LOH patterns between the HCC and ICC components was greater than 30%, suggesting different clonal origins of HCC and ICC. Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC (P < 0.05).ConclusionsOur results suggest that the HCC and ICC components of CHC may originate from the same clone, having the potential for dual-directional differentiation similar to HPCs. CHC tended to exhibit the biological behaviors of both HCC and ICC, which may enhance the infiltrative capacity of tumor cells, leading to poor clinical outcomes for patients with CHC.
Highlights
Combined hepatocellular and cholangiocarcinoma (CHC) is a unique subtype of liver cancer com‐ prising both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC); its cellular origin remains unclear
Between January 1982 and December 2009, of 31,000 cases of primary hepatic carcinoma treated at the Eastern Hepatobiliary Surgery Hospital (EHBH) in Shanghai, China, 92.3%, 6.7%, and 1.9% were classified as HCC, ICC, and CHC, respectively [5]
The male-to-female ratios for CHC, separated HCC and ICC (SHC), pure HCC, and pure ICC groups were 7.5:1, 6.3:1, 15.6:1, and 2.3:1, respectively, with men being the predominant sex in all groups
Summary
Combined hepatocellular and cholangiocarcinoma (CHC) is a unique subtype of liver cancer com‐ prising both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC); its cellular origin remains unclear. The purpose of this study was to investigate the clinicopathologic features and the clonal relation‐ ship between HCC and ICC in 34 patients with CHC. Combined hepatocellular and cholangiocarcinoma (CHC), which is characterized by hepatocellular and biliary epithelial differentiation within the same tumor [1,2,3], is a unique type of primary hepatic carcinoma that is distinct from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Between January 1982 and December 2009, of 31,000 cases of primary hepatic carcinoma treated at the Eastern Hepatobiliary Surgery Hospital (EHBH) in Shanghai, China, 92.3%, 6.7%, and 1.9% were classified as HCC, ICC, and CHC, respectively [5]. Molecular alterations in CHC have not been extensively studied, and the clonal link between the HCC and ICC components of CHC remains unclear [4, 6,7,8,9,10,11,12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
