Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma

Abstract

Expression of phenotype markers of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) in HCC and CC components of 20 combined hepatocellular and cholangiocarcinomas (CHCs) of the liver was investigated immunohistochemically. Both HCC and CC components of all CHCs expressed at least one of the CC phenotype markers [cytokeratin (CK)-7, CK-19, and carbohydrate (CA) 19-9]. HCC components in 90% of CHCs and CC components in 95% of CHCs expressed at least one of these CC phenotype markers in more than 40% of cancer cells. HCC components in all CHCs expressed at least one of the HCC phenotype markers [hepatocyte antigen (HA), α-fetoprotein (AFP), and canalicular carcinoembryonic antigen]. HCC components in 90% of CHCs and CC components in 75% of CHCs expressed HA, AFP, or both. HCC components in 75% of CHCs and CC components in 60% of CHCs expressed HA, AFP, or both in more than 10% of cancer cells. The present results show that both HCC and CC components of most of the CHCs expressed both HCC and CC phenotypes, supporting the hypothesis that CHC originates from a hepatic progenitor cell capable of differentiating into hepatocytes and cholangiocytes.

A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma

“…Biomarkers previously associated with HCC-CC were confirmed in this study and included: AFP, CEA, GGT1, cytokeratin, mucin and metalloproteinase genes (7)(8)(9)(10)(12)(13)(14)(15)19). Among these biomarkers, GGT, AFP, and CEA have been non-specific in the setting of HCC-CC (25).…”

“…Among these biomarkers, GGT, AFP, and CEA have been non-specific in the setting of HCC-CC (25). In contrast, cytokeratin, mucin production, and metalloproteinase molecules appear to be valuable to the diagnosis and prognosis of HCC-CC (7)(8)(9)(10)(12)(13)(14)(15)19,25). Specifically, they appear to be useful in differentiating between classical and stem cell subtypes of HCC-CC.…”

“…Specifically, they appear to be useful in differentiating between classical and stem cell subtypes of HCC-CC. Such determinations can be facilitated utilizing cytokeratin signaling biomarkers (7)(8)(9)(10)(12)(13)(14)(15)19,25). These serologic markers also appear to be useful in colorectal and breast neoplasms, with similar application (40).…”

“…Although this entity does demonstrate pathologic features of its well-established biphenotypic counterparts, the characteristics of this neoplasm make diagnosis challenging using conventional radiologic imaging and serologic markers. Moreover, accurate prognostic information is affected by the low frequency of this tumor, which restricts available clinical information even within Original Article A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma large medical centers (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…Prior studies have examined the role of cytoskeletal stability, apoptosis, and the inflammatory cascade in HCC-CC (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Additionally, as HCC-CC poses a diagnostic dilemma for radiologists, tumor specific biomarker may assist in the diagnosis of this neoplasm and prognostic assessment (23,24).…”