Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular localisation of the polymeric Ig receptor (pIg-R) and carcinoembryonic antigen (CEA), hepatic and biliary cell markers, were investigated in patients with hepatocellular carcinoma (HCC) and high serum levels of secretory component. Serum SC were increased 6-20-fold in 8 HCC patients compared with normal subjects. Serum free SC was positively correlated bilirubin (r = 0.95, P less than 0.04). In normal liver tissue, cytokeratin (CK) 8 and 18 were localised in hepatocytes and biliary cells while pIg-R and CK 19 expression was restricted to biliary cells. In tumoral liver tissue, malignant cells expressed CK 8 and 18 weakly; pIg-R and CK 19 were not detected in tumoral cells. CEA was expressed by biliary cells in normal and proliferating ducts. In peritumoral fibrosis, proliferating biliary cells were strongly stained by anti-cytokeratins and anti-pIg-R antibodies. In one case, pIg-R was localised in isolated cells close to fibrosis without co-staining of anti-CK 19. Thus increased serum SC is not associated with pIg-R expression by tumoral cells, and pIg-R may be considered an additional marker of biliary cells. High SC might be explained either by reflux from bile to serum and/or release of unbound SC from the vascular pole of non-functional, proliferating biliary structures.
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PMID:Polymeric Ig receptor expression in hepatocellular carcinoma. 137 92

The early stages of the carcinogenic process induced by aflatoxin B1 (AFB1) in rat liver during 24 weeks of feeding and the resulting tumours have been studied with respect to cytokeratin (CK) expression. A previously uncharacterized monoclonal antibody, MRCTU/J1, has been shown to recognize rat CK18 and together with antibodies against human CK8, 18 and 19, has been used to examine the possible lineage of tumour cells and also to identify the altered foci that might be most relevant to tumorigenesis. Results suggested that AFB1-induced transformation in liver may occur in more than one cell type, since tumours with the normal hepatocyte CK pattern and those with bile duct or oval cell CK phenotype were identified. Additionally, hepatocytes with a bile duct CK phenotype appeared during the early stages of carcinogenesis. The in vivo pattern of CK expression also appeared to be maintained in one normal and one hepatoma-derived cell line. Overexpression of CKs (particularly of CK19) was a much more selective marker for altered foci, compared to gamma-glutamyltranspeptidase, and was more consistently expressed at high levels in tumours, suggesting that it might be a more reliable way of identifying those cells involved in the transformation process.
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PMID:Cytokeratin expression during AFB1-induced carcinogenesis. 169 54

Six cases of primary hepatic carcinomas with a significant amount of sarcomatoid elements were examined by using immunohistochemical stainings. Four of the six cases were associated with ordinary hepatocellular carcinoma (HCC), one with cholangiocellular carcinoma (CCC), and one with mixed HCC and CCC. Alpha-fetoprotein and alpha-1-antitrypsin were negative in sarcomatoid cells of all cases; vimentin stained positively in sarcomatoid tumor cells in two of the six cases; and cytokeratin (CK8) was detected in five cases. The CK8 was not detected in tumor cells of two cases of hepatic angiosarcoma, two of metastatic leiomyosarcomas, and one of metastatic fibrosarcoma, although vimentin stained positively in all these true sarcomas. It was concluded that sarcomatoid dedifferentiation of liver carcinomas might derive from both HCC and CCC. In addition CK8 might be an excellent marker to make a differential diagnosis of sarcomatoid cancers from true metastatic or primary sarcomas of the liver.
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PMID:An immunohistochemical study of sarcomatoid liver carcinomas. 171 Sep 48

A combined hepatocellular-cholangiocarcinoma (CHC) of transitional subtype and the surrounding cirrhotic liver tissue were investigated immunocytochemically by monoclonal antibodies specific for each of the keratin polypeptides 7, 8, 18 and 19. Different keratin subsets were found in different parts of the tumour. The hepatocellular component reveals keratins 8 and 18, with the bordering cells of trabecular formations additionally expressing keratins 7 and 19. The same keratins i.e. 7, 8, 18, 19 were found in normal bile duct epithelium as well as in cholangiocarcinomatous and transitional areas of hepatocellular and cholangiocellular differentiation. Normal hepatocytes express only keratin 8 and 18. In cirrhotic liver some modified hepatocytes additionally express keratin 7. When ductal transformation is observed in the marginal parts of portal tracts and fibrous septa the keratin polypeptide pattern mimics that of bile duct epithelium. The cholangiocellular metaplasia of hepatocytes observed here correlates well with findings in hepato-organogenesis and hepatocarcinogenesis and suggests that the transitional subtype of combined hepatocellular-cholangiocarcinoma is a variant of hepatocellular carcinoma.
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PMID:Evidence for a hepatocellular lineage in a combined hepatocellular-cholangiocarcinoma of transitional type. 246 36

Plasminogen binding to cell surfaces may be important for tumor invasion and other processes that involve cellular migration. In this investigation, the principal plasminogen-binding protein was identified in the plasma membrane fraction of rat hepatocytes. The protein had an apparent mass of 59 kDa, was insoluble in a spectrum of detergents, and was identical to cytokeratin 8 (CK 8) as determined by sequence analysis of nine amino acids at the N terminus of two cyanogen bromide fragments. The 59 kDa protein bound CK 8-specific antibody in western blot analyses. These studies demonstrate that CK 8 or a CK 8-like protein binds plasminogen. Given this newly determined and potentially important CK 8 function, immunofluorescence and immunoelectron microscopy studies were performed to determine whether CK 8 may be present on the external surfaces of unpermeabilized, viable hepatocytes. All of the cells in each preparation were immunopositive with two separate CK 8-specific antibodies. A punctate pattern of immunofluorescence was detected on the cell surface with approximately even intensity from cell to cell. By immunoelectron microscopy, CK 8 was preferentially associated with microvilli. In order to determine whether other epithelial cells express cell-surface CK 8, immunofluorescence and immunoelectron microscopy studies were performed with HepG2 hepatocellular carcinoma cells and with BT20 and MCF-7 breast carcinoma cells. The pattern of antigen expression was equivalent with each cell type and comparable to that observed with hepatocytes. These studies support the hypothesis that CK 8 is associated with the external cell surface where it may express important proteinase receptor function.
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PMID:A cytokeratin 8-like protein with plasminogen-binding activity is present on the external surfaces of hepatocytes, HepG2 cells and breast carcinoma cell lines. 754 67

To assess the utility of cytokeratin (CK) profile and albumin mRNA detection (as revealed by in situ hybridization) in the differential diagnosis of primary liver carcinomas (PLCs) we evaluated a series of surgically resected PLCs, comprising 20 "pure" hepatocellular carcinomas (HCCs) (10 well-differentiated, 10 poorly differentiated), 15 cholangiocarcinomas (CCs) (6 peripheral, 5 hilar, and 4 major duct ones) and 10 hepatocholangio-carcinomas (HCC-CCs). 11 of 20 (55%) of the pure HCCs expressed CKs of pure hepatocytic lineage (CK 8 and CK 18); 2 of 10 (20%) of the HCC-CCs displayed only hepatocytic profile, whereas 12 of 15 (80%) of the CCs evidenced mature bile duct cell phenotype (CK 8, CK 18, CK 7, CK 19). All HCCs expressed varying distributions of albumin mRNA, whereas 4 of 6 (67%) peripheral CCs showed cells with focal positivity for albumin mRNA. This suggests that the phenotypic expression of PLC cells are often not fixed, and in particular: (1) peripheral CCs have a different phenotype from hilar and large duct ones; (2) the CK profile and albumin mRNA expression in peripheral CCs show many similarities with those of some HCCs. Furthermore, the results show that a mixed biological phenotype (ie, CK 8, CK 18 and CK 7 and/or CK 19) can be found both among morphologically pure HCCs and peripheral CCs, suggesting that these two forms could share a common histogenesis. We think that special attention should be given to cases in which CK profile and albumin mRNA reveal mixed phenotype, as these tumors could have different biological behavior and respond differently to therapy.
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PMID:Histogenesis of primary liver carcinomas: strengths and weaknesses of cytokeratin profile and albumin mRNA detection. 866 72

During experiments to identify putative hepatic receptors for thrombin-antithrombin (TAT) complexes, a 45-kDa protein was identified by ligand blotting. Following gel purification, amino acid sequencing revealed the 45-kDa TAT-binding polypeptide to be cytokeratin 18 (CK18). The presence of CK18 on the surface of intact rat hepatoma cells was demonstrated by binding of 125I-anti-CK18 antibodies. Anti-CK18 antibodies reduced the binding and internalization of 125I-TAT by rat hepatoma cells. Immunocytochemical analysis, to determine the location of CK18 in vivo, revealed a periportal gradient of CK18 staining; with hepatocytes around the portal triads demonstrating striking pericellular staining. In addition, anti-CK18 IgG associated with perfused livers to a significantly greater extent than preimmune IgG. Taken together, these data provide evidence that CK18 is found on the extracellular surface of hepatocytes and could play a role in TAT removal. Finally, these data, in conjunction with recent reports of CK8 (Hembrough, T. A., Li, L., and Gonias, S. L. (1996) J. Biol. Chem. 271, 25684-25691) and CK1 cell membrane surface expression (Schmaier, A. H. (1997) Thromb. Hemostasis 78, 101-107), indicate a novel role for these proteins as putative cellular receptors or cofactors to cellular receptors.
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PMID:Cytokeratin 18 is expressed on the hepatocyte plasma membrane surface and interacts with thrombin-antithrombin complexes. 935 22

Immunocytochemistry has indicated that, in the liver, the bcl-2 gene is generally expressed in bile duct cells and tumors of biliary origin. Both in situ hybridization and immunocytochemistry were used to analyze the expression of bcl-2 messenger RNA (mRNA) and its protein product (Bcl-2) in the tissue of 50 pure primary liver tumor (PLT) specimens including 40 hepatocellular carcinoma (HCC) specimens and 10 cholangiocellular carcinoma (CC) specimens. The phenotype of the tumors expressing bcl-2 was confirmed by immunocytochemical assessment of the cytokeratin (CK) profile (CK8, CK18, CK7, and CK19). Whereas positive immunoreaction with the anti-Bcl-2 MoAb was revealed in only 8 (20%) of 40 HCC specimens and 1 (10%) of 10 CC specimens, high contents of bcl-2 mRNA were found in 26 (65%) of 40 HCC specimens and 9 (90%) of 10 CC specimens. Regarding the CK profile, only 25 (62%) of 40 HCC specimens showed pure hepatocytic lineage (CKs 8-18), whereas among the remaining 15 HCC specimens, positivity for either CK7 (12 specimens) or CK19 (5 specimens) was observed. All 10 CC specimens stained with CKs 8-18-19, and 8 of 10 stained with CK 7 as well. These results indicate that PLTs display a greater expression of bcl-2 mRNA than of the Bcl-2 protein. Furthermore, CK profile assessment confirmed that bcl-2 expression is not confined to liver tumors of biliary origin. In the absence of a well-demonstrated post-transcriptional control of the gene, the authors propose the detection of bcl-2 mRNA by in situ hybridization as a possible alternative method for assessing the expression of bcl-2 mRNA in PLT.
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PMID:High levels of BCL-2 messenger RNA detected by in situ hybridization in human hepatocellular and cholangiocellular carcinomas. 1061 75

Spontaneous hepatic neoplasms were identified in two adolescent (<5 years of age) male cynomolgus monkeys (Macaca fascicularis). Monkey No. 1 had a solitary hepatocellular carcinoma (HCC). Monkey No. 2 had multiple discrete tumors consisting of several poorly circumscribed HCCs and a mixed hepatocholangiocellular carcinoma (MHC). Metastases were not evident in either monkey. Histochemical and immunohistochemical stains were used to assess phenotypic alterations in the tumors. Many or most neoplastic hepatocytes (NHs) of both monkeys stained positive for low-molecular-weight cytokeratin (LMWCK), cytokeratin (CK) 8, and CK 18. In monkey No. 1, small aggregates of NHs were positive for carcinoembryonic antigen (CEA), glutathione S-transferase-pi (GST), and alpha-fetoprotein (AFP), but NHs were uniformly negative for CK 7. NHs in monkey No. 2 were negative for CEA and AFP but were multifocally positive for GST and CK 7. Broad-spectrum cytokeratin (BSCK), high-molecular-weight cytokeratin (HMWCK), and CK 19 did not react with NHs of either animal. Neoplastic cells forming ductlike structures in the MHC of monkey No. 2 stained with LMWCK, CK 7, CK8, CK 18, BSCK, and GST but not with HMWCK or CK 19. Tumors in both monkeys had enhanced pericellular fibronectin staining. Nonneoplastic parenchyma of both monkeys contained multiple discrete foci of cellular alteration and scattered aggregates of hepatocytes with strong cytoplasmic staining for fibronectin. Staining patterns of these tumors demonstrate immunophenotypic heterogeneity of the neoplastic cells within individual tumors and variability among tumors. This information may serve as a useful reference for others encountering similar lesions in primates.
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PMID:Spontaneously occurring hepatocellular neoplasia in adolescent cynomolgus monkeys (Macaca fascicularis). 1110 57

We clinicopathologically studied 6 resected cases of cholangiolocarcinoma (CLC) including 2 referred cases from other hospitals. The frequency of CLC was 0.56% of the 708 consecutively resected cases of primary liver cancer and the mean age of CLC cases was 66 years. Three of the 6 cases (50%) were hepatitis C virus antibody (HCVab) positive, one (17%) was hepatitis B virus surface antigen (HBsAg) positive, and 2 (33%) were negative to both HCVAb and HBsAg. Serum levels of alpha-fetoprotein were slightly elavated only in 1 case. Clinically, 4 cases were diagnosed as hepatocellular carcinoma (HCC) and 2 cases as cholangiocellular carcinoma (CCC). Grossly, CLCs were whitish in color and solid, not encapsulated, and resembled CCC. Histologically, the tumor cells had eosinophilic cytoplasm with ovoid nuclei, and mild atypia. The tumor proliferated in an anastomosing pattern of Hering's canal-like small glands with an abundant fibrous stroma. Four of the 6 tumors (83%) consisted of only CLC and other 2 tumors contained CCC-like area and HCC-like area in a part of the nodules, respectively. Immunohistochemically, all tumors were positive to cytokeratin (CK) 7. CK8 were also positive in all of 6 cases. These results revealed that CLC had the clinical features resembling HCC but the morphologic features resembling CCC. It is suggested that CLC cells might be derived from Hering's canal or stem cells which have the intermediate features between hepatocytes and bile duct epithelium.
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PMID:Clinicopathologic study on cholangiolocellular carcinoma. 1118 37


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