A Clinicopathological study on combined hepatocellular and cholangiocarcinoma

Abstract

We clinicopathologically studied 23 surgically resected cases of combined hepatocellular and cholangiocarcinoma (HCC-CC). The frequency of this cancer in our subjects, who had primary liver cancer and who underwent hepatectomy, was 6.3%. The mean age of patients was 64.0 years old and the male: female ratio was 1.9:1. Serum alpha-fetoprotein was positive in 70% of cases and its levels were relatively low (< or = 1000 ng/mL) in most cases. The positive rate of serum carcinoembryonic antigen was 18% and its levels were also low. In regard to hepatitis virus markers, 17% of the 20 combined HCC-CC cases were positive to HBs antigen and 70% were positive to the HCV antibody. Of the 23 combined HCC-CC cases, 9 cases (39%) were associated with liver cirrhosis. Tumours were classified macroscopically into a separated type (HCC and CC are clearly separated 17%), a HCC-predominant type (resembles HCC 49%), and a CC-predominant type (resembles CC 34%). The separated and HCC-predominant types were associated with liver cirrhosis in 50 and 55% of cases, respectively. These cases with liver cirrhosis presented the features of HCC more apparently, while those without liver cirrhosis presented the features of CC. Histologically, all cases were classified into either Type I (HCC and CC were clearly distinguished; 17%), Type II (HCC and CC were contiguous and shared transitional features; 66%), and Type III (cancer cells were able to be evaluated as either HCC or CC and were considered to be an intermediate type; 17%). Immunohistological stains for cytokeratin were useful to distinguish HCC and CC. Specifically, CC was positive to cytokeratin 7 and 19. The tumour, in which HCC and CC were almost indistinguishable, such as Type III), indicates the presence of intermediate tumour cells that can differentiate either to HCC or CC.

Proteomic signature corresponding to alpha fetoprotein expression in liver cancer cells

“…10 These pathological and clinical features could be explained by a common protein network with AFP expression. Taking annexin A1 as an example, this protein is a major substrate for tyrosine kinases such as epidermal growth factor receptor and serine/threonine kinases such as protein kinase C 43,44 and has been implicated in cellular signal transduction. 45 Enhanced expression of annexin A1 was observed in poorly differentiated HCC tissues compared with their well-differentiated counterparts, and the nontumorous region contained significantly lower amounts of annexin A1, suggesting that annexin A1 is related to the histological grade of HCC and is involved in the malignant transformation process.…”

Primary liver carcinoma of intermediate (hepatocyte–cholangiocyte) phenotype

“…However, there have been a few reported cases in the literature of combined hepatocellular-cholangiocarcinomas (CHCs) [1 -4], a subset of primary liver carcinomas suggested to arise from transformed progenitor cells which have the bipotential to differentiate into both hepatocytes and cholangiocytes. Taguchi et al [3] classified CHC into three types: (i) type I, in which there were clearly separable areas of HCC and CC; (ii) type II, in which the HCC and CC areas were contiguous with an intervening area of transition; and (iii) type III, in which the tumor was not readily classifiable as HCC or CC, and were composed of tumor cells showing morphological features intermediate between HCC and CC. Robrechts et al [5] reported a case of 'liver tumor of intermediate (hepatocyte-bile duct cell) phenotype', consisting of small cells with a phenotype intermediate between hepatocytes and cholangiocytes and simultaneously expressing cytokeratins (CK) 7, 8, 18 and 19.…”

Cytokeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver cancer

“…In Japan and east Asia, chronic HCV infection has been linked to a high incidence of ICC, including combined hepato-cholangiocellular carcinoma (c-HCC-CC) (Tomimatsu et al, 1993;Shin et al, 1996;Su et al, 1996;Taguchi et al, 1996;Yamamoto et al, 1998). Follow-up of patients with HCV infection therefore can detect many cases of ICC as well as HCC.…”