bromochloroacetic-acid has been researched along with Carcinoma--Hepatocellular* in 172 studies
10 review(s) available for bromochloroacetic-acid and Carcinoma--Hepatocellular
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New therapeutic strategy for hepatocellular carcinoma by molecular targeting agents via inhibition of cellular stress defense mechanisms.
The prognosis of advanced hepatocellular carcinoma (HCC) has remained very poor.It has recently been reported that the molecular targeting agent sorafenib can improve the prognosis of patients with advanced HCC. However, the detailed mechanisms of sorafenib, especially its direct effects on hepatoma and hepatocyte cells, are poorly understood, making a more detailed investigation about the molecular mechanism of sorafenib necessary. Endoplasmic reticulum (ER) stress is related to the pathophysiology of various liver diseases, including chronic viral hepatitis, alcoholic and nonalcoholic steatohepatitis and HCC. In this regard, our recent data examining the molecular effects of sorafenib focused on the cellular defense mechanisms from ER stress, the unfolded protein response (UPR) and keratin phosphorylation, demonstrated that sorafenib inhibited both important cytoprotective mechanisms, UPR and keratin phosphorylation, and enhances the anti-tumor effect in combination with proteasome inhibitors. This review summarizes the cytoprotective mechanisms from ER stress and our results about the direct effect of sorafenib on the cytoprotective mechanisms. Topics: Antineoplastic Agents; Autophagy; Carcinoma, Hepatocellular; Cytoprotection; Drug Therapy, Combination; Endoplasmic Reticulum Stress; Humans; Keratins; Liver Neoplasms; Molecular Targeted Therapy; Niacinamide; Phenylurea Compounds; Phosphorylation; Prognosis; Proteasome Inhibitors; Sorafenib; Unfolded Protein Response | 2014 |
Hepatoid variant of pancreatic cancer: insights from a case and literature review.
"Hepatoid" cancer refers to an extrahepatic neoplasm with hepatocellular differentiation. The stomach is the most common site and pancreatic origin is distinctly uncommon.. We describe a patient with hepatoid pancreatic tumor who presented with inoperable metastatic disease.. Serum levels or tissue staining with alpha-fetoprotein (AFP) may not be a reliable tumor marker in these cases and an experienced pathologist and appropriate immunohistochemical staining are essential for early diagnosis. This report incorporates a comprehensive literature review outlining the clinical presentation, diagnostic difficulties, management and outcomes associated with this rare pathological entity. Topics: alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers; CA-19-9 Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Hepatocytes; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Vimentin | 2013 |
Ectopic hepatocellular carcinoma arising from pancreas: a case report and review of the literature.
A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed an encapsulated, rather heterogeneous, hypoechoic tumor, 6.5 cm in maximum diameter, with a beak sign. Helical dynamic CT revealed an irregularly enhanced tumor with pooling of contrast medium in the delayed phase. Abdominal angiography showed a hypervascular tumor. With a tentative diagnosis of non-functional islet-cell tumor, the patient underwent resection of the pancreatic body and tail with splenectomy. The contour of the liver and its surface were normal. In microscopic examination, tumor cells arranged in a trabecular pattern with focal bile pigment resembling hepatocellular carcinoma (HCC). Immunohistochemically, these tumor cells were positivefor HEPPAR-1, CAM5.2, cytokeratin 18 and COX-2, but negative for MUC-1, and cytokeratins 7, 20 and 8. These results supported a diagnosis of HCC without any adenocarcinoma component. The patient is currently doing well without any signs of recurrence in either the remaining pancreas or liver three years after surgery. We report the rare case with ectopic HCC in the pancreas with a review of the literature. Topics: Angiography; Biomarkers; Carcinoma, Hepatocellular; Choristoma; Humans; Keratin-18; Keratins; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Tomography, X-Ray Computed | 2007 |
Management of patients with metastatic cancer of unknown primary.
Topics: Adenocarcinoma; Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cytogenetic Analysis; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Lymphatic Metastasis; Magnetic Resonance Imaging; Mesothelioma; Neoplasm Metastasis; Neoplasms, Unknown Primary; Peritoneal Neoplasms; Positron-Emission Tomography; Prognosis; Rhabdomyosarcoma; Tomography, X-Ray Computed; Urinary Bladder Neoplasms | 2005 |
A decade's studies on metastasis of hepatocellular carcinoma.
Metastasis remains one of the major challenges before hepatocellular carcinoma (HCC) is finally conquered. This paper summarized a decade's studies on HCC metastasis at the Liver Cancer Institute of Fudan University. We have established a stepwise metastatic human HCC model system, which included a metastatic HCC model in nude mice (LCI-D20), a HCC cell line with high metastatic potential (MHCC97), a relatively low metastatic potential cell clone (MHCC97L) and several stepwise high metastatic potential cell clones (MHCC97H, HCCLM3, and HCCLM6) from their parent MHCC97 cell. Endeavors have been made for searching human HCC metastasis-related chromosomes/proteins/genes. Monogene-based studies revealed that HCC invasion/metastasis was similar to that of other solid tumors, and the biological characteristics of small HCC were only slightly better than that of large HCC. Using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), genotyping, cDNA microarray, and 2-dimensional gel electrophoresis, we obtained some interesting results. In particular, in collaboration with the National Institute of Health (NIH) in the United States, we generated a molecular signature that can classify metastatic HCC patients, identified osteopontin as a lead gene in the signature, and found that genes favoring metastasis progression were initiated in the primary tumors. We also found that chromosome 8p deletion, particularly in the region of 8p23, was associated with HCC metastasis. Cytokeratin 19 was identified as one of the proteins, which was found in MHCC97H, but not in MHCC97L cells. Experimental interventions using the high metastatic nude mice model have provided clues for the prevention of HCC metastasis. Translation from workbench to bedside demonstrated that serum VEGF, microvessel density, and p53 scoring may be of value for the prediction of postoperative metastatic recurrence. Interferon alpha proved effective for the prevention of recurrence both experimentally and clinically. In conclusion, HCC metastasis that probably initiated in the primary tumor is a multigene-involved, multistep, and changing process. The further elucidation of the mechanism underlying HCC metastasis will provide a more solid basis for the prediction and prevention of the metastatic recurrence of HCC. Topics: Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Line, Tumor; Chromosomes, Human, Pair 8; DNA, Complementary; DNA, Neoplasm; Electrophoresis, Gel, Two-Dimensional; Gene Deletion; Genotype; Humans; In Situ Hybridization, Fluorescence; Keratins; Liver Neoplasms; Liver Neoplasms, Experimental; Mice; Mice, Nude; Microcirculation; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; Predictive Value of Tests; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A | 2004 |
[Biomarkers for neoplasmas in digestive organs].
This review is concerned with the usefulness and the problem of biomarkers for cancer of digestive organs. Carcinoembryonic antigen (CEA) is a most popular and useful tumor marker for cancer of digestive organs. Squamous cell carcinoma (SCC) antigen and CYFRA have been reported as a useful tumor marker for esophageal cancer. CEA and CA 19-9 are a good prognostic factor in gastric cancer patients. The post-operative increase of serum CEA can be a predictive marker for the patients of colorectal cancer. Development of a radioimmunoassay for highly sensitive detection of tumor markers, they are considered to be useful for monitoring after treatment. But are not useful for the early diagnosis. The diagnosis of hepatocellular carcinoma (HCC) is based mainly on serological markers, such as alpha-fetoprotein and PIVKA-II. The two are useful complementary markers of HCC because they do not correlate with each other. But the problem of the false-positive rate for the patients with chronic hepatitis or liver cirrhosis is still remained. A typical marker of pancreatic and bile duct cancer is carbohydrate antigen, but the sensitivity of these markers is only 50%. Recent molecular biological analysis may be used as effective biomarkers in the diagnosis, prognosis, therapy, and risk assessment of digestive cancer. Topics: alpha-Fetoproteins; Antigens, CD19; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Colorectal Neoplasms; Digestive System Neoplasms; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Lewis X Antigen; Liver Neoplasms; Pancreatic Neoplasms; Prognosis; Protein Precursors; Prothrombin; Stomach Neoplasms | 2004 |
Spontaneously occurring hepatocellular neoplasia in adolescent cynomolgus monkeys (Macaca fascicularis).
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. Topics: alpha-Fetoproteins; Animals; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholangiocarcinoma; Glutathione Transferase; Immunohistochemistry; Keratins; Liver Neoplasms; Macaca fascicularis; Male; Monkey Diseases | 2000 |
Hepatocellular carcinoma with chondrosarcomatous variation: case report with immunohistochemical findings, and review of the literature.
Hepatocellular carcinoma with chondrosarcomatous variation is very rare. We report a case with the results of pathology examination, and review the literature. The patient, a 72-year-old may had a very large tumor in the liver revealed during follow-up for diabetes mellitus. The liver mass, which was 14 cm in diameter, was diagnosed as hepatocellular carcinoma by abdominal ultrasonography. Anterior segmentectomy and partial liver resection were performed. Histopathology examination revealed that the tumor consisted of two different components: the major one was hepatocellular carcinoma (HCC), which occupied most of the tumor; and a sarcomatous component, which occupied a smaller area, and included spindle-shaped cells with chondroscarcomatous variation. Intrahepatic metastases and tumor thrombi of HCC were also found in portal and hepatic veins. Investigations of the immunohistochemical localization of keratin (KRT), vimentin (VMT), and S-100 protein (S 100) were performed by the avidin-biotin complex method. Some of the spindle cells were immunohistochemically positive for both KRT and VMT, and the chondrosarcomatous cells were positive for S 100. These results strongly suggested that the sarcomatous lesion resulted from a sarcomatous change of HCC. Topics: Aged; Biomarkers, Tumor; Carcinoma, Hepatocellular; Chondrosarcoma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; S100 Proteins; Vimentin | 1998 |
[Hepatic neoductules].
Proliferation of preexisting bile ducts, ductular metaplasia of hepatocytes and proliferation and differentiation of liver stem cells are discussed in the pathogenesis of neoductular structures in the liver. Under the condition of experimental bile duct obstruction and in extrahepatic bile duct stenosis neoductular structures are first the result of proliferation and sprouting of preexisting ducts and cholangioles. Especially in later stages of cholestasis but also in other chronic progredient liver diseases such as chronic alcoholic liver disease and chronic active hepatitis periportal hepatocytes may show a phenotypic shift towards ductular epithelia. In postnatal liver diseases hepatocytes first express keratin 7 and later keratin 19 during ductular transdifferentiation. This is in contrast to embryonal cholangiogenesis. In alpha-1-antitrypsin-deficiency, hemochromatosis, Wilson's disease, and chronic active hepatitis B cellular deposites typically located in hepatocytes such as alpha-1-AT, siderin, copper, HBs-Ag, and HBc-Ag can also be found in neoductular cells close to hepatocytes. These deposites seem to be retained during the ductular transdifferentiation of hepatocytes. Expression of bile duct-type integrin subtypes and TGF beta 1 in neoductular cells are involved in the changing parenchymal/mesenchymal interplay during neoductogenesis, resulting in periductular basal membrane and periductular fibrosis. In FNH the ductular transdifferentiation of hepatocytes is integrated in the histogenesis of micronodules and portal tract equivalents of these tumor-like lesions. Ductular structures in hepatoblastomas and especially in combined hepatocellular and cholangiocarcinomas (CHCC) may reflect the common embryologic derivation of hepatocytes and biliary epithelia. Non-neoplastic liver tissue in resection specimens of our CHCC showed a lower rate of cirrhosis, and a significantly higher Ki 67-LI of neoductular cells compared to liver tissue in resection specimens of HCC and liver metastases. 3 of 10 CHCC had developed in alpha-1-AT-deficiency, in which this protease-inhibitor was predominantly retained in periportal hepatocytes. These findings in non-neoplastic tumor-bearing liver tissue suggest that CHCC include a special histogenic type of primary liver carcinoma which in analogy to some experimental liver tumors might develop from periportal parenchymal cells. Topics: alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Animals; Bile Ducts; Bile Ducts, Extrahepatic; Carcinoma, Hepatocellular; Cell Differentiation; Cell Division; Cholangiocarcinoma; Cholestasis; Copper; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Hepatoblastoma; Humans; Hyperplasia; Keratins; Liver; Liver Diseases; Liver Neoplasms; Metaplasia | 1995 |
Present understanding of the development of Mallory's body.
Mallory's body filament assembly includes polypeptides of the cytokeratin class of intermediate filaments and also higher molecular weight polypeptides normally found only in the cytokeratins of mature keratinocytes of the epidermis. These additional polypeptides may alter both the morphologic characteristics and increase the resistance to dissolution of the filaments by Ca++-activated protease activity. Thus, it is likely that the kinetics of Mallory's body filament assembly and dissolution favor growth of the filaments. In rodents fed certain carcinogens, Mallory's body formation has been accompanied by the induction of the oncofetoenzyme gamma-glutamyl transpeptidase (GGT), suggesting that Mallory's body formation, like GGT induction, is a phenotypic change related to the process of neoplastic transformation in rodents. Topics: Animals; Carcinogens; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cytoskeleton; gamma-Glutamyltransferase; Griseofulvin; Humans; Intermediate Filament Proteins; Keratins; Liver; Liver Diseases; Liver Neoplasms; Liver Neoplasms, Experimental; Lung; Lung Diseases; Phosphorylation; Protein Precursors | 1983 |
1 trial(s) available for bromochloroacetic-acid and Carcinoma--Hepatocellular
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Selective transitional zone sampling approach versus random biopsy in cases with malignant liver masses: is there any superiority?
Currently, the diagnostic sensitivity of malignant liver mass biopsies is an important problem in the definitive diagnosis. In this study, we aimed to investigate the role of selective peripheral approach to lesion biopsies for diagnostic sensitivity of liver masses.. Between June 2007 and March 2011, totally 88 patients (50 male, 38 female), referred to our Interventional Radiology Department for sonographically guided Tru-cut biopsies for liver lesions, were examined.All biopsies were performed by an experienced radiologist with an 18-gauge Tru-cut biopsy needle with a spring-loaded biopsy gun under sonographic guidance. We describe two locations (peripheral and central) for liver lesions, with the inner 2/3 part of the mass as central and the outer 1/3 part as peripheral. We obtained biopsy from both of these locations, and samples were transferred to the Pathology Department separately.. According to pathological and immunohistochemistry studies, there were 42 hepatocellular carcinomas and 46 metastases. All of the metastatic tumors were stained by cytokeratin (10 lung adenocarcinoma, 15 breast adenocarcinoma, 16 gastrointestinal tract, 4 prostate, and 1 malignant melanoma of these 46 metastases were reported as primary). According to histopathological results, diagnostic sensitivity was 97.7% in peripherally located biopsies and 86.3% in biopsies taken from the center of the masses (p=0.0063).. Selective peripheral biopsy approach in Tru-cut biopsies of liver lesions has better sensitivity rates for histopathologic diagnosis compared to the centrally located and random biopsies. Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Carcinoma, Hepatocellular; Creatine Kinase; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Humans; Keratins; Liver Cirrhosis; Liver Neoplasms; Lung Neoplasms; Male; Melanoma; Middle Aged; Prostatic Neoplasms; Sensitivity and Specificity; Skin Neoplasms | 2012 |
161 other study(ies) available for bromochloroacetic-acid and Carcinoma--Hepatocellular
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Hepatoid prostatic carcinoma with adrenal metastasis and novel genetic alterations.
Hepatoid carcinoma (HC) encompasses epithelial extrahepatic tumors exhibiting features of hepatocellular carcinoma (HCC) both by morphology and immunohistochemistry. Distinguishing metastatic HCC from HC may be challenging, particularly when limited material, such as a cytologic specimen, is available. HC from prostatic origin is unusual and has only rarely been characterized by cytology. Herein we present an 86-year-old male with history of castration-resistant prostate cancer developing a left adrenal gland nodule. Fine needle aspiration revealed a poorly differentiated malignant neoplasm diagnosed as metastatic hepatoid prostatic adenocarcinoma based on immunohistochemistry (positive for HepPar1, AFP, NKX3.1, PSMA, and Racemase; and negative for CK7, CK20, cytokeratin 34betaE12, p63, and Arg-1). Because prostatic carcinoma with hepatoid features is rare, and the patient had failed standard therapy, next generation sequencing was performed in an attempt to identify druggable molecular targets. Well-known prostate carcinoma-related alterations were found in three genes (CDK12, AR, and SPOP). In addition, three variants of uncertain significance (DDR2 R128C, SRC P428L, and HNRNPU K574Sfs*32) were identified, which to the best of our knowledge have not been previously reported. Our results support the power of an immunohistochemistry panel including Arg-1 and HepPar1 when HC is suspected, and highlight the value of cytology for comprehensive diagnostic evaluation. Topics: Adenocarcinoma; Aged, 80 and over; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Keratins; Liver Neoplasms; Male; Nuclear Proteins; Prostate; Prostatic Neoplasms; Racemases and Epimerases; Repressor Proteins | 2022 |
Keratin 23 Is a Peroxisome Proliferator-Activated Receptor Alpha-Dependent, MYC-Amplified Oncogene That Promotes Hepatocyte Proliferation.
Chronic activation of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARA) promotes MYC-linked hepatocellular carcinoma (HCC) in mice. Recent studies have shown that MYC can function as an amplifier of transcription where MYC does not act as an "on-off" switch for gene expression but rather accelerates transcription rates at active promoters by stimulating transcript elongation. Considering the possibility that MYC may amplify the expression of PPARA target genes to potentiate cell proliferation and liver cancer, gene expression was analyzed from livers of wild-type and liver-specific Myc knockout (Myc Topics: Animals; Carcinoma, Hepatocellular; Cell Proliferation; Female; Gene Expression Regulation; Hepatocytes; Humans; Keratins; Keratins, Type I; Liver Neoplasms; Male; Mice; Oncogene Protein p55(v-myc); PPAR alpha | 2019 |
Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver.
Keratin proteins form intermediate filaments, which provide structural support for many tissues. Multiple keratin family members are reported to be associated with the progression of liver disease of multiple etiologies. For example, keratin 23 (KRT23) was reported as a stress-inducible protein, whose expression levels correlate with the severity of liver disease. Hepatitis C virus (HCV) is a human pathogen that causes chronic liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. However, a link between KRT23 and hepatitis C virus (HCV) infection has not been reported previously. In this study, we investigated KRT23 mRNA levels in datasets from liver biopsies of chronic hepatitis C (CHC) patients and in primary human hepatocytes experimentally infected with HCV, in addition to hepatoma cells. Interestingly, in each of these specimens, we observed an HCV-dependent increase of mRNA levels. Importantly, the KRT23 protein levels in patient plasma decreased upon viral clearance. Ectopic expression of KRT23 enhanced HCV infection; however, CRIPSPR/Cas9-mediated knockout did not show altered replication efficiency. Taken together, our study identifies KRT23 as a novel, virus-induced host-factor for hepatitis C virus. Topics: Carcinoma, Hepatocellular; Cell Line; HEK293 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Host-Derived Cellular Factors; Host-Pathogen Interactions; Humans; Keratins; Keratins, Type I; Liver; Liver Cirrhosis; Liver Neoplasms; RNA, Messenger; Transcriptome; Virus Replication | 2019 |
Synchronous hepatocellular carcinoma and lymphoepithelioma-like carcinoma arising from 2 different sites of the liver: A case report.
Most cases of primary liver cancer involve hepatocellular carcinoma (HCC). Lymphoepithelioma-like carcinoma (LELC) is defined as a tumor composed of undifferentiated epithelial cells with a prominent lymphoid infiltrate, which is rarely reported. Lymphoepithelioma-like HCC (LEL-HCC) is an uncommon variant of HCC, having an unclear process of development. Here, we report the first case involving simultaneous HCC and LEL-HCC.. A 77-year-old female was accidentally found to have a hypoechoic hepatic nodule via an abdominal ultrasound during a health examination. Abdominal computed tomography scan revealed 2 hepatic nodules with arterial phase enhancement and washout in the late phase.. We diagnosed the case with 2 distinct liver nodules, HCC and LEL-HCC.. With suspicion of HCC, tumor resection (liver segments 4 and 5) was then performed. Histopathological examination of tumor 1 showed a moderately differentiated HCC and tumor 2 demonstrated a LEL-HCC. Immunohistochemically, the cells of tumor 2 were immunoreactive for cytokeratin (CK), CK7, and CK19. Epstein-Barr virus encoding small RNA (EBER) in situ hybridization results were negative.. Six months after resection, intrahepatic tumor recurrence was noted. Radiofrequency ablation was conducted.. This is an interesting case providing circumstantial evidence of simultaneous development of HCC and LEL-HCC in distinct nodules of the liver with a background of chronic hepatitis B virus infection. Topics: Aged; Carcinoma, Hepatocellular; Female; Hepatitis B, Chronic; Humans; Keratins; Liver Neoplasms | 2018 |
The expression of arginase-1, keratin (K) 8 and K18 in combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type.
The WHO classification describes that combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell subtype (CHC-INT) is composed of tumour cells with features intermediate between hepatocytes and cholangiocytes. However, we previously reported that CHC-INT showed a high positive rate of biliary markers, but the expression of hepatocyte paraffin (HepPar)-1 was low. In this study, we examined the expression of other hepatocyte markers, such as arginase-1 (Arg-1), keratin (K) 8 and K18 in CHC-INT in order to examine the utility of pathological diagnosis in CHC-INT.. We performed immunohistochemistry (IHC) of Arg-1, K8 and K18 using 32 previously diagnosed as CHC-INT. Immunoreactivity was evaluated with grading from 0 to 4 according to the distribution area of positive cells. The obtained findings of Arg-1, K8 and K18 were compared with those of K7, K19 and HepPar-1.. Out of the 32 cases, 22 (68.8%) cases were positive for Arg-1. Twenty-five (78.1%) were positive for K8. The IHC scores of Arg-1 and K8 were significantly higher than those of HepPar-1, but significantly lower than those of K7 and K19. The K18 expression was widely observed in all cases (100%). The IHC score of Arg-1 and K8 in CHC-INT was intermediate between hepatocellular carcinoma and cholangiocarcinoma.. Arg-1 and K8 were good markers to identify intermediate cells between hepatocytes and cholangiocytes. These can be useful markers for pathological diagnosis of CHC-INT, which usually has wide histological diversities, in combination with other hepatocytic and/or cholangiocytic markers. Topics: Aged; Arginase; Bile Duct Neoplasms; Biomarkers; Carcinoma, Hepatocellular; Cholangiocarcinoma; Female; Gene Expression Regulation, Neoplastic; Hepatocytes; Humans; Immunohistochemistry; Immunophenotyping; Keratin-18; Keratin-8; Keratins; Liver; Liver Neoplasms; Male; Middle Aged | 2016 |
HCC-DETECT: a combination of nuclear, cytoplasmic, and oncofetal proteins as biomarkers for hepatocellular carcinoma.
Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy. Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Nucleus; Cytoplasm; Female; Humans; Keratins; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Nuclear Matrix-Associated Proteins; ROC Curve; Sensitivity and Specificity | 2015 |
Detection of circulating tumor cells in hepatocellular carcinoma using antibodies against asialoglycoprotein receptor, carbamoyl phosphate synthetase 1 and pan-cytokeratin.
Asialoglycoprotein receptor (ASGPR)-ligand-based separation combined with identification with Hep Par 1 or pan-cytokeratin (P-CK) antibody have been demonstrated to detect circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC). The aim of this study was to develop an improved enrichment and identification system that allows the detection of all types of HCC CTCs.. The specificity of the prepared anti-ASGPR monoclonal antibody was characterized. HCC cells were bound by ASGPR antibody and subsequently magnetically isolated by second antibody-coated magnetic beads. Isolated HCC cells were identified by immunofluorescence staining using a combination of anti-P-CK and anti-carbamoyl phosphate synthetase 1 (CPS1) antibodies. Blood samples spiked with HepG2 cells were used to determine recovery and sensitivity. CTCs were detected in blood samples from HCC patients and other patients.. ASGPR was exclusively expressed in human hepatoma cell line, normal hepatocytes and HCC cells in tissue specimens detected by the ASGPR antibody staining. More HCC cells could be identified by the antibody cocktail for CPS1 and P-CK compared with a single antibody. The current approach obtained a higher recovery rate of HepG2 cells and more CTC detection from HCC patients than the previous method. Using the current method CTCs were detected in 89% of HCC patients and no CTCs were found in the other test subjects.. Our anti-ASGPR antibody could be used for specific and efficient HCC CTC enrichment, and anti-P-CK combined with anti-CPS1 antibodies is superior to identification with one antibody alone in the sensitivity for HCC CTC detection. Topics: Animals; Antibodies; Asialoglycoprotein Receptor; Carbamoyl-Phosphate Synthase (Ammonia); Carcinoma, Hepatocellular; Cell Line, Tumor; Female; Humans; Keratins; Liver Neoplasms; Mice, Inbred BALB C; Neoplastic Cells, Circulating | 2014 |
Sorafenib enhances proteasome inhibitor-mediated cytotoxicity via inhibition of unfolded protein response and keratin phosphorylation.
Hepatocellular carcinoma (HCC) is highly resistant to conventional systemic therapies and prognosis for advanced HCC patients remains poor. Recent studies of the molecular mechanisms responsible for tumor initiation and progression have identified several potential molecular targets in HCC. Sorafenib is a multi-kinase inhibitor shown to have survival benefits in advanced HCC. It acts by inhibiting the serine/threonine kinases and the receptor type tyrosine kinases. In preclinical experiments sorafenib had anti-proliferative activity in hepatoma cells and it reduced tumor angiogenesis and increased apoptosis. Here, we demonstrate for the first time that the cytotoxic mechanisms of sorafenib include its inhibitory effects on protein ubiquitination, unfolded protein response (UPR) and keratin phosphorylation in response to endoplasmic reticulum (ER) stress. Moreover, we show that combined treatment with sorafenib and proteasome inhibitors (PIs) synergistically induced a marked increase in cell death in hepatoma- and hepatocyte-derived cells. These observations may open the way to potentially interesting treatment combinations that may augment the effect of sorafenib, possibly including drugs that promote ER stress. Because sorafenib blocked the cellular defense mechanisms against hepatotoxic injury not only in hepatoma cells but also in hepatocyte-derived cells, we must be careful to avoid severe liver injury. Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Death; Cell Line, Tumor; Drug Synergism; Endoplasmic Reticulum Stress; Humans; Keratins; Liver Neoplasms; Niacinamide; Phenylurea Compounds; Phosphorylation; Proteasome Inhibitors; Sorafenib; Ubiquitination; Unfolded Protein Response | 2013 |
Metastatic hepatocellular carcinoma presenting as a maxillary sinus mass; a fine needle aspiration cytology diagnosis.
Topics: Aged; Biomarkers, Tumor; Biopsy, Fine-Needle; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Maxillary Sinus Neoplasms; Neprilysin; Orbital Neoplasms; Papanicolaou Test | 2013 |
Clinical and pathological analysis of 27 patients with combined hepatocellular-cholangiocarcinoma in an Asian center.
Our purpose was to assess the clinicopathological features and surgical outcomes of combined hepatocellular-cholangiocarcinoma (HCC-CC) in an Asian center.. Between 1998 and 2009, 27 patients were diagnosed with combined HCC-CC at our hospital. Their medical records were reviewed and clinicopathological data retrospectively analyzed.. The 27 patients included 24 (88.9%) males and 3 (11.1%) females with a mean age of 58.26 ± 11.18 years. Cirrhosis was present in 10 patients (37.0%), and 12 patients had hepatitis C or hepatitis B virus infection. Serum alpha fetoprotein was >20 ng/ml in 7 of the 19 patients in whom it was measured (36.8%). Twenty-five patients underwent hepatic resections and 2 received liver transplantations. Five (18.5%) patients had separate HCC and CC within the same liver (type I), 21 (77.8%) had tumors with mixed components (type II), and 1 patient had a type III tumor (3.7%). Of 22 patients with immunohistochemical data, 19 (86.4%) were cytokeratin (CK) 7-positive, 20 (90.9%) were CK19-positive, and 4 (18.2%) were CK20-positive. Mean follow-up was 25.8 months. The 1- and 2-year survival rates were 72.5 and 49.4%, respectively. The 1- and 2-year disease-free survival rates were 54.2 and 41.3%, respectively. Symptoms at the time of diagnosis, and regional lymph node metastases, were associated with higher mortality and recurrence.. Lymph node metastasis and positive resection margins are important factors affecting HCC-CC surgical outcomes. Topics: Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Multiple Primary; Prognosis; Retrospective Studies | 2012 |
Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase.
Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in PDAC, an epithelial-to-mesenchymal transition (EMT) is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN) and the tumor cell transition, biopsies of patients with PDAC (n = 115) were analysed with regard to PMN infiltration and nuclear expression of β-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation of β-catenin and of ZEB1 was observed. To address the question whether PMN could induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated, β-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMT in vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction of EMT and-by implication-to tumor progression is possible. Topics: Adult; Aged; Aged, 80 and over; beta Catenin; Biopsy; Cadherins; Carcinoma, Hepatocellular; Carcinoma, Pancreatic Ductal; Cell Adhesion; Cell Line, Tumor; Cell Nucleus; Epithelial-Mesenchymal Transition; Female; Homeodomain Proteins; Humans; Keratins; Leukocyte Elastase; Liver Neoplasms; Male; Middle Aged; Neutrophils; Nuclear Proteins; Organic Cation Transport Proteins; Pancreatic Neoplasms; Transcription Factors; Twist-Related Protein 1; Zinc Finger E-box-Binding Homeobox 1 | 2012 |
Claudins and tricellulin in fibrolamellar hepatocellular carcinoma.
Fibrolamellar hepatocellular carcinoma is a subtype of hepatocellular carcinoma occurring in non-cirrhotic liver at a younger age. The tumor expresses both hepatocellular and cholangiocellular markers. Previously, our group described overexpression of tight junction protein claudin 4 in cholangiocellular carcinoma in contrast to hepatocellular carcinoma. In the present study, tight junction protein expressions were studied to possibly clarify bipotential lineage of fibrolamellar hepatocellular carcinoma. Eleven fibrolamellar hepatocellular carcinomas were compared with seven "conventional" hepatocellular carcinomas, seven cholangiocellular carcinomas, and five normal liver samples. By immunohistochemistry, all fibrolamellar hepatocellular carcinomas were positive for HepPar1 and cytokeratins 7, 8, and 18, but negative for cytokeratin 19. Glypican-3 gave weak staining in two cases. Expression of claudin 1 was lower, while that of claudin 2 was higher in fibrolamellar hepatocellular carcinomas than in other tumors. Claudins 3, 4, and 7 were not detectable in fibrolamellar hepatocellular carcinomas as in the majority of "conventional" hepatocellular carcinomas, contrary to high expression observed in cholangiocellular carcinomas. Focal or diffuse claudin 5 expression was detected in nine of 11 fibrolamellar hepatocellular carcinomas contrary to other tumors. Tricellulin was significantly downregulated in all tumors compared with normal liver. Our findings showed claudins to exhibit specific expression patterns in fibrolamellar hepatocellular carcinomas not observed in other primary liver tumors, with unique claudin 5 expression and pattern features similar to common hepatocellular carcinoma, but different from cholangiocellular carcinoma. This is the first report describing the loss of tricellulin expression in human hepatic tumors. Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Hepatocellular; Child; Cholangiocarcinoma; Claudins; Female; Glypicans; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; MARVEL Domain Containing 2 Protein; Membrane Proteins; Middle Aged; Retrospective Studies; Young Adult | 2011 |
Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition.
Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells.. We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization.. These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT. Topics: Cadherins; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Down-Regulation; Epithelial-Mesenchymal Transition; Focal Adhesion Kinase 2; Focal Adhesions; Humans; Keratins; Liver Neoplasms; Microscopy, Electron, Scanning; STAT5 Transcription Factor | 2011 |
Evaluation of cytokeratin-1 in the diagnosis of hepatocellular carcinoma.
This study was undertaken to investigate whether serum cytokeratin-1 (CK1) could complement alpha-fetoprotein (AFP) to improve the diagnosis of hepatocellular carcinoma (HCC).. CK1 was identified using western blot and ELISA in serum samples from 250 Egyptian patients including 150 with HCC, 100 with liver cirrhosis (LC) and 50 healthy controls. Multivariate discriminant analysis (MDA) and ROC curve analyses were used to create a predictive model including CK1 in addition to a panel of routine blood markers.. CK1 was identified at 67 kDa and quantified in sera of HCC patients using western blot and ELISA. MDA selected a score for the prediction of HCC from LC patients based on levels of CK1, albumin and AFP. An area under the ROC curves (AUC) of the score was 0.87. The score showed a sensitivity of 87% vs 39% sensitivity of AFP at cutoff value of 200 IU/ml for prediction HCC. Absolute specificity (100%) was obtained to discriminate HCC from healthy individuals.. This study suggests that the use of a combination of score including CK1, AFP and albumin in clinical practice provides a non invasive and simple test that could increase significantly the sensitivity of HCC diagnosis. Topics: Blotting, Western; Carcinoma, Hepatocellular; Enzyme-Linked Immunosorbent Assay; Humans; Keratins; Liver Neoplasms; Middle Aged; Multivariate Analysis; ROC Curve | 2011 |
Tripartite components of a hepatocellular carcinoma with distinct immunohistochemical and metastatic features.
We report an unusual case of hepatocellular carcinoma with three histologically and immunohistochemically distinct components, arising in a noncirrhotic liver, with a pulmonary tumor embolus from one of the three components. The histological patterns of the three components were fibrolamellar, well-differentiated nodular, and pleomorphic. The immunophenotypes were, respectively CK7- /CK20- /Hep Par1+, CK7+ /CK20- /Hep Par1+, and CK7+ /CK20+ /Hep Par1-. The tumor in the pulmonary embolus showed only the morphological and immunohistochemical features of the pleomorphic component. This unusual case ofmetastasizing hepatocellular carcinoma with three distinct histologic components suggests that the histological and immunophenotype of the tumor might be useful in predicting metastatic potential. Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Hepatocellular; Diagnosis, Differential; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Lung Neoplasms; Male; Neoplastic Cells, Circulating | 2010 |
Fibrolamellar hepatocellular carcinoma: an immunohistochemical comparison with conventional hepatocellular carcinoma.
The fibrolamellar variant of hepatocellular carcinoma (FLC) differs from conventional hepatocellular carcinoma (HCC) in some clinical and pathological features. The authors investigated possible differences in reactivity between FLCs and HCCs using glypican-3 (GPC3), an oncofetal protein, and survivin, an antiapoptotic protein. They also compared staining of FLC and HCC with antibodies to cytokeratins 7 (CK7) and 19 (CK19) and CD34. GPC3 was significantly more often and more strongly expressed in HCCs (72%) than in FLCs (17%). Survivin nuclear translocation in tumor cells did not differ between HCCs (10%) and FLCs (9%). There was more abundant expression of CK7 in FLCs (92%) than in HCCs (33%), whereas CK19 was more often found in HCCs (20%) than in FLCs (5%). All tumors had CD34-positive sinusoids. This study shows that FLCs and HCCs differ in the expression of GPC3, CK7, and CK19 and that there is a lack of difference as regards survivin and CD34. Topics: Antigens, CD34; Biomarkers, Tumor; Carcinoma, Hepatocellular; Glypicans; Humans; Immunoenzyme Techniques; Inhibitor of Apoptosis Proteins; Keratin-19; Keratin-7; Keratins; Liver Neoplasms; Microtubule-Associated Proteins; Neoplasm Proteins; Survivin | 2010 |
Metastatic hepatocellular carcinoma of skin diagnosed with hepatocyte paraffin 1 and a-fetoprotein immunostainings.
A rare case of skin metastasis of hepatocellular carcinoma diagnosed with an aid of immunohistochemical stainings of hepatocyte paraffin 1 and a-fetoprotein is reported in this study. An 86-year-old Japanese man was admitted to our hospital due to cutaneous mass in the right chest. An incisional biopsy was performed, which showed proliferation of malignant cells with eosinophilic or clear cytoplasm arranged in solid nests. No trabecular pattern was recognized. Sebaceous carcinoma, clear cell sarcoma, malignant granular cell tumor, metastatic renal cell carcinoma, and metastatic hepatocellular carcinoma were suspected on hematoxylin and eosin preparations. An immunohistochemical study showed that the tumor cells were positive for cytokeratins, hepatocyte paraffin 1, and a-fetoprotein but negative for vimentin, desmin, a-smooth muscle actin, S-100 protein, epithelial membrane antigen, carcinoembryonic antigen, chromogranin, neuron-specific enolase, CD10, CD30, CD34, CD45, CD68, and HMB45. Metastatic hepatocellular carcinoma of the skin was diagnosed pathologically. This case suggests that skin tumors with eosinophilic cytoplasm should be examined by hepatocyte paraffin 1 and a-fetoprotein. Topics: Aged, 80 and over; alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Hepatocellular; Hepatocytes; Humans; Keratins; Liver Neoplasms; Male; Skin Neoplasms | 2010 |
Is histological diagnosis of primary liver carcinomas with fibrous stroma reproducible among experts?
In the era of targeted therapeutics, histological typing of hepatobiliary carcinomas has major clinical implications. Little is known about the reproducibility of the pathological diagnosis of primary liver carcinomas. Therefore, this study aimed to evaluate the worldwide variation in the pathological expert diagnoses of primary liver carcinomas with fibrous stroma in patients who did not have cirrhosis.. A single set of slides was selected from 25 tumours, and this set was reviewed independently by 12 pathologists who have worldwide expertise in liver tumours. Reproducibility of the diagnoses was evaluated by Light's kappa, and diagnoses were clustered by multidimensional scaling. Immunohistochemistry was performed after histological review.. The interobserver reproducibility for diagnosis of hepatocellular carcinoma subtypes and cholangiocarcinomas was poor (kappa 0.23-0.52), even when the experts considered that the diagnosis required no additional stains or clinical information. Interestingly, multidimensional scaling revealed three main clusters of tumours: hepatocellular carcinoma with no other specifications (n = 13), fibrolamellar hepatocellular carcinoma (n = 3) and cholangiocarcinoma (n = 9). Using immunohistochemistry, these histological clusters correlated with expression of anti-hepatocyte and anti-cytokeratin 19 (p<0.001).. The results demonstrate the poor reproducibility among experts of the pathological diagnosis of primary liver carcinomas with fibrous stroma in patients who did not have cirrhosis, and highlight that the systematic use of immunohistochemistry may improve the diagnostic accuracy. Topics: Adolescent; Adult; Aged; Antibodies; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Child; Cholangiocarcinoma; Cluster Analysis; Diagnosis, Differential; Female; Hepatocytes; Humans; Immunohistochemistry; Keratin-19; Keratin-7; Keratins; Liver Neoplasms; Male; Medical Oncology; Middle Aged; Reproducibility of Results; Young Adult | 2009 |
Epithelioid angiomyolipoma of the liver with striking giant cell component: fine-needle aspiration biopsy findings of a rare neoplasm.
Angiomyolipoma (AML) is a uncommon benign neoplasm of the liver with cyto- and histologic features similar to the more commonly encountered renal AML. Tumors composed predominantly of epithelioid cells have been referred to as epithelioid AML. Because most liver lesions are first evaluated by fine-needle aspiration biopsy (FNAB), it is important to distinguish this variant of AML from more common hepatic neoplasms such as hepatocellular carcinoma (HCC) or metastatic tumors. Rare reports of epithelioid AML of the liver diagnosed by FNAB are in the literature. Here, we describe the cytologic findings of a unique case of epithelioid AML with numerous giant cells. Topics: Actins; Angiomyolipoma; Antigens, Neoplasm; Biopsy, Fine-Needle; Carcinoma, Hepatocellular; Diagnosis, Differential; Female; Giant Cells; Humans; Keratins; Liver Neoplasms; Melanoma-Specific Antigens; Neoplasm Proteins; S100 Proteins; Young Adult | 2009 |
Hepatoid esophageal carcinoma: a rare cause of elevated alpha fetoprotein.
AFP-producing tumors are uncommon. They have mostly been described of pulmonary origin. However, they have also been described from gastrointestinal tract. Esophageal involvement with hepatoid tumor has been rarely described. The diagnosis is clinically challenging in patients with metastatic disease to liver. We present an interesting case of AFP-producing esophageal tumor, describing its clinical presentation, endoscopic manifestation, as well as histological features. Topics: alpha-Fetoproteins; Carcinoma, Hepatocellular; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged | 2008 |
Biliary neoplasia with extensive intraductal spread associated with liver cirrhosis: a hitherto unreported variant of biliary intraepithelial neoplasia.
We describe the histopathologic features of 2 cases of biliary neoplasia with extensive intraductal spread arising in liver cirrhosis. The prevalence of this type of biliary neoplasia may be 0.4% from the review of 468 cases of cirrhotic liver. Histologic analysis revealed that the micropapillary proliferation of the atypical biliary epithelium composed of columnar cells with enlarged nuclei diffusely extended superficially from the septal intrahepatic bile duct to the reactive ductules associated with liver cirrhosis. Both cases exhibited prominent fibrous or sclerotic stroma near the biliary lesion. Immunohistochemical analysis revealed a characteristic cytokeratin and mucin expression pattern (CK7++, CK19++, CK20+, MUC1+/-, MUC2-, MUC5AC+, MUC6-). The tumor cytoplasm was focally positive for laminin gamma2 together with linear staining of the basement membrane. Proliferative activity confirmed by Ki67 staining was relatively high. Both patients were disease-free for 3 years after the operation. We believe that the possibility of biliary neoplasia with extensive intraductal spread should be considered to be a variant of biliary intraepithelial neoplasia. Topics: Bile Ducts, Intrahepatic; Biliary Tract Neoplasms; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Count; Cell Proliferation; Cholangiocarcinoma; Hepatitis C, Chronic; Humans; Immunoenzyme Techniques; Keratins; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Middle Aged; Mucins; Neoplasms, Multiple Primary; Treatment Outcome | 2008 |
A subgroup of intrahepatic cholangiocarcinoma with an infiltrating replacement growth pattern and a resemblance to reactive proliferating bile ductules: 'bile ductular carcinoma'.
The histogenesis and biological behaviour of peripheral intrahepatic cholangiocarcinoma (peripheral CC) remain unclarified. The aim of this study was to examine the growth pattern of peripheral CC (24 cases) in comparison with hepatocellular carcinoma (HCC, 27 cases) and metastatic colorectal adenocarcinoma (MCA, 24 cases).. Tumour/surrounding liver borders were classified as: (i) fibrous encapsulation, (ii) compressive growth, and (iii) infiltrating replacement. Nineteen of 24 peripheral CCs showed (iii), whereas 23 of 27 HCCs showed (i) and 17 of 24 MCAs showed (ii). In (iii), carcinoma cells infiltrated the surrounding liver without compression, and hepatic supporting vascular structures such as portal tracts were secondarily incorporated into the tumour. In (i) and (ii), the surrounding liver was compressed and no or few portal tracts were incorporated within the tumour. Fifteen of 24 peripheral CCs were composed of carcinoma cells resembling reactive bile ductules and these cells were positive for neural cell adhesion molecule (NCAM), a marker of proliferating bile ductules. The remaining nine peripheral CCs were composed of ordinary adenocarcinoma and negative for NCAM.. A subgroup of peripheral CCs with an infiltrating replacement growth pattern resembles reactive bile ductules and expresses NCAM. 'Bile ductular carcinoma' may be a better term for this subgroup. Topics: Adenocarcinoma; Aged; Aged, 80 and over; Autopsy; Bile Duct Neoplasms; Bile Ducts; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; CD56 Antigen; Cholangiocarcinoma; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Male; Middle Aged; Neural Cell Adhesion Molecules; Organ Size; Vimentin | 2007 |
Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas.
The recently identified claudins are dominant components of tight junctions, responsible for cell adhesion, polarity and paracellular permeability. Certain claudins have been shown to have relevance in tumor development, with some of them, especially claudin-4, even suggested as future therapeutic target. The aim of the present study was to analyze the expression of claudin-4 in the biliary tree, biliary tract cancers and hepatocellular carcinomas. A total of 107 cases were studied: 53 biliary tract cancers, 50 hepatocellular carcinomas, 10 normal liver and 10 normal extrahepatic biliary duct samples. Immunohistochemical analysis was performed on conventional specimens and on tissue microarrays as well. Claudin-4 was further investigated by Western blot analysis and real-time RT-PCR. Intense membranous immunolabeling was found for claudin-4 in all biliary tract cancers unrelated to the primary site of origin, namely intrahepatic, extrahepatic or gallbladder cancers. Normal biliary epithelium showed weak positivity for claudin-4. In contrast, normal hepatocytes and tumor cells of hepatocellular carcinomas did not express claudin-4. The results of Western immunoblot analysis and real-time RT-PCR were in correlation with the immunohistochemical findings. Cytokeratins, as CK7 (92%) and CK19 (83%) were mostly positive in biliary tract cancers, however, one-third of hepatocellular carcinomas also expressed CK7 (34%). HSA antibody (HepPar1) reacted with the majority of hepatocellular carcinomas (86%), while being positive in a low percentage of the biliary tract cancers (8%). In conclusion, this is the first report of a significantly increased claudin-4 expression in biliary tract cancers, which represents a novel feature of tumors of biliary tract origin. Claudin-4 expression seems to be a useful marker in differentiating biliary tract cancers from hepatocellular carcinomas and could well become a potential diagnostic tool. Topics: Adenocarcinoma; Biliary Tract Neoplasms; Blotting, Western; Carcinoma, Hepatocellular; Claudin-4; Diagnosis, Differential; Gene Expression; Humans; Immunohistochemistry; Keratin-7; Keratins; Laminin; Liver; Liver Neoplasms; Membrane Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tissue Array Analysis | 2006 |
Are the Mallory bodies and intracellular hyaline bodies in neoplastic and non-neoplastic hepatocytes related?
Mallory bodies (MBs) and intracellular hyaline bodies (IHBs) are cytoplasmic hepatocellular inclusions that consist of aggregated proteins. MBs are characteristically associated with alcoholic and non-alcoholic steatohepatitis, but may also be found in chronic cholestatic and metabolic (eg copper intoxication) diseases and hepatocellular neoplasms, particularly hepatocellular carcinomas. IHBs have hitherto only been described in hepatocellular carcinoma cells. In the present study hepatocellular carcinomas (HCCs) and a case of idiopathic copper toxicosis were evaluated with respect to the presence and mutual relationship of MBs and IHBs. IHBs alone were present in 8.6%, MBs alone in 16.1% and both types of inclusion in 7.5% of HCCs. It is shown that IHBs may also occur in non-neoplastic hepatocytes in association with idiopathic copper toxicosis, together with MBs. In HCCs and idiopathic copper toxicosis, MBs and IHBs may be present within the same cell. Moreover, hybrid inclusions holding an intermediate position between MBs and IHBs regarding light microscopy, ultrastructure and composition exist. MBs and IHBs contain p62, a stress-inducible adapter protein, as the major constituent. In MBs p62 is associated with keratins, whereas classical IHBs lack keratins. Light microscopic, electron microscopic and immunohistochemical data suggest a close pathogenetic relationship between MBs and IHBs. Both types of inclusion are the result of over-expression and accumulation of the stress protein p62. If p62 is induced alone, or at least prevails, IHBs may arise by aggregation. However, if abnormal keratins are present in addition to p62, p62 associates and co-aggregates with keratins, finally leading to classical MBs. Topics: Adaptor Proteins, Signal Transducing; Carcinoma, Hepatocellular; Chemical and Drug Induced Liver Injury; Copper; Hepatocytes; Humans; Hyalin; Inclusion Bodies; Keratins; Liver Diseases; Liver Neoplasms; Microscopy, Electron; Microscopy, Immunoelectron; Neoplasm Proteins; Sequestosome-1 Protein | 2006 |
Cytoplasmic staining of TTF-1 in the differential diagnosis of hepatocellular carcinoma vs cholangiocarcinoma and metastatic carcinoma of the liver.
The cytoplasmic staining of thyroid transcription factor (TTF)-1 was analyzed in 86 liver resection specimens, including 40 hepatocellular carcinoma (HCC), 4 metastatic HCC, 20 cholangiocarcinoma, 2 combined hepatocellular-cholangiocarcinoma (CHC), and 20 metastatic carcinoma (MC) specimens with immunohistochemical stains to TTF-1, cytokeratin (CK)19, hepatocyte paraffin 1, alpha-fetoprotein, polyclonal carcinoembryonic antigen, CK7, and CK20. TTF-1 cytoplasmic staining was identified in 93% of HCCs (37/40), 100% of metastatic HCCs (4/4), 10% of cholangiocarcinomas (2/20), and 5% of MCs (1/20). CK19 was positive in all cholangiocarcinomas and MCs but only in 5% of HCCs (2/40) and none of the metastatic HCCs (0/4). TTF-1 cytoplasmic staining positively correlates with differentiation and the trabecular growth pattern of HCC. The results suggest TTF-1 cytoplasmic staining, together with CK19, might serve as a useful marker for the diagnosis of primary and metastatic HCC and for the differential diagnosis of HCC from cholangiocarcinoma and MC. The mechanism of TTF-1 cytoplasmic staining is explored. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Cytoplasm; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors | 2006 |
The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas.
To study the differences between the hepatocellular carcinoma (HCC) and peripheral type of cholangiocarcinoma (CHC) using cytokeratin (CK) and carcinoembryonic antigen (CEA) expressions and assessing their accuracy on paraffin sections in the differential diagnosis.. The following antibodies were analyzed: AB1 complex (anti CK9-CK20), AB2 complex (anti CK1-CK8), pCEA, and the monoclonal antibodies against cytokeratins CK7, CK8/18, CK17 and CK19. In the mmunohistochemical studies, 15 selected surgically resected liver tumors, 10 HCCs and 5 CHCs, with well established diagnosis (by morphological criteria) were included. Other markers, such as AFP si CA 19-9, were not available.. No CHC, but 50% of HCCs were positive for CEA, presenting a canalicular staining pattern. For CK 7, all but one (which was focally positive), meaning 80% of CHCs were diffusely positive, whereas only two HCCs were positive. For CK 19, 80% of CHCs were diffusely positive, while all but two HCCs (a moderately and a poorly differentiated tumor) were negative. For CK 8/18, 70% of HCCs were diffusely positive, whereas only 20% of CHCs were positive. For CK 17, 60% of CHCs were positive, while all HCCs were negative. 80% of CHCs were positive for AB1 anti-CKs complex, whereas only 50% of HCCs were positive, and relating to AB2 anti-CKs complex, 50% of HCCs were diffusely positive and only 20% of CHCs.. The immunohistochemical expression of CKs and CEA might be considered helpful in addition to other diagnostic criteria for the differential diagnosis of primary carcinomas of the liver, especially in difficult cases. Topics: Adolescent; Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Retrospective Studies | 2006 |
Adenomyoma with goblet and Paneth cells of the ileum.
A case of ileal adenomyoma with goblet and Paneth cells is reported. A 75-year-old man died of ruptured hepatocellular carcinoma. As an incidental finding at autopsy, a 9 x 7 x 6 mm(3)-sized nodule was found in the ileal wall. Histologically, the lesion occupied the submucosa and muscularis propria, and consisted of glandular structures of various sizes and interlacing smooth muscle bundles surrounding the glandular elements. Goblet cells and Paneth cells were interspersed in the glandular element. Immunohistochemically, the glandular element was positive for cytokeratin (CK) 7 and negative for CK 20. This is the first reported case of adenomyoma of the gastrointestinal tract that contained Paneth cells. The result of the immunohistochemical staining favored the heterotopic pancreas theory concerning its pathogenesis. The appearance of goblet and Paneth cells might be the result of metaplasia. Topics: Adenomyoma; Aged; Biomarkers, Tumor; Carcinoma, Hepatocellular; Fatal Outcome; Goblet Cells; Humans; Ileal Neoplasms; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Liver Neoplasms; Male; Neoplasms, Second Primary; Paneth Cells; Rupture, Spontaneous | 2006 |
Clinical significance of serum cytokeratin-19 fragment (CYFRA 21-1) in hepatocellular carcinoma.
CYFRA 21-1, a soluble fragment of cytokeratin 19, is increased in serum in some patients with hepatocellular carcinoma, but the clinical significance of this increase is still unknown.. Serum concentrations of CYFRA 21-1 were measured in 240 patients with hepatocellular carcinoma prior to hepatic resection. The relationships between serum CYFRA 21-1 concentrations and clinicopathologic features were analyzed.. The sensitivity of CYFRA 21-1 as a test for hepatocellular carcinoma was 18.8%. Serum CYFRA 21-1 was significantly higher in patients with portal vein tumor thrombus, and serum CYFRA 21-1 increased with the progression of portal vein tumor thrombus. Tumor size was related to serum CYFRA 21-1, but there were no significant correlations between serum CYFRA 21-1 concentrations and tumor differentiation or number of tumors. Although patients with stage IV tumor had significantly higher CYFRA 21-1 concentrations than those with stages I, II, and III, CYFRA 21-1 was not associated with postoperative prognosis.. Although high concentrations of CYFRA 21-1 were often detected in patients with a tumor diameter greater than 5 cm or tumor thrombus in the major portal vein, CYFRA 21-1 is not a useful diagnostic tool for hepatocellular carcinoma because of its low sensitivity. Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Humans; Keratin-19; Keratins; Liver Neoplasms; Male; Middle Aged; Sensitivity and Specificity | 2006 |
Clinicopathological implications of immunohistochemically demonstrated mucin core protein expression in hepatocellular carcinoma.
We examined the expression of mucin core protein 1 (MUC1) immunohistochemically in 186 surgical specimens of histopathologically nonmucinous hepatocellular carcinoma (HCC) and compared the clinicopathological features in patients with MUC1-positive HCC (MUC1-positive group) with those in patients with MUC1-negative HCC (MUC1-negative group).. MUC1 immunoreactively was present in 85 of the 186 HCCs. Of the clinicopathological variables examined, the serum concentration of alpha-fetoprotein, tumor differentiation, bile duct invasion, lymph node metastasis, and cytokeratin 19 expression exhibited significant associations with MUC1 expression. Although cumulative and tumor-free survival rates were not different between the two groups, the percentage of patients with first recurrence of HCC in distant organs (distant metastasis) within 2 years after surgery was significantly higher in the MUC1-positive group than in the MUC1-negative group (P = 0.0104). The risk ratio of MUC1 positivity for this type of distant metastasis was 3.156 (95% confidence interval, 1.064-9.358).. In patients with MUC1-positive HCC, careful follow-up is necessary, not only for intrahepatic recurrence but also for distant metastasis, after the resection of primary HCC. Topics: Adult; Aged; Antigens, Neoplasm; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Mucin-1; Mucins; Neoplasm Invasiveness; Neoplasm Metastasis; Survival Analysis; Viral Core Proteins | 2006 |
Serum CYFRA 21-1 level reflects hepatocellular carcinoma metastasis: study in nude mice model and clinical patients.
Our previous proteomics study on human hepatocellular carcinoma (HCC) cell strains revealed that cytokeratin 19 (CK19) was expressed in cells with high metastasis potential; we further studied serum CK19 fragment CYFRA 21-1 level in HCC patients and nude mice model of HCC metastasis. HCC cell line HCCLM3 was injected subcutaneously into 30 nude mice which were then randomized into 6 groups of 5 mice each. The murine serum CYFRA 21-1 and pulmonary metastases were determined 2, 3, 4, 5, 6, and 7 weeks after injection. Serum CYFRA 21-1 levels of 101 normal controls and 108 HCC patients were also determined. In nude mice model, CYFRA 21-1 level increased significantly when pulmonary metastases occurred. Among 108 HCC patients, 24 (22.2%) had increased serum CYFRA 21-1 level. The presence of portal vein tumor emboli was significantly higher in CYFRA 21-1 increased cases (33.3%, 6/24) than in CYFRA 21-1 normal cases (6.0%, 5/84) (x2=7.403, P < 0.01). In addition, the percentage of TNM stage III/IV tumor was significantly higher in CYFRA 21-1 increased patients (54.2%, 13/24) than in CYFRA 21-1 normal cases (21.4%, 18/84) (x2=9.776, P < 0.005). These results suggest that CK19 may play an important role in HCC metastasis. Topics: Adult; Aged; Animals; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Humans; Keratin-19; Keratins; Liver Neoplasms; Lung Neoplasms; Male; Mice; Mice, Nude; Middle Aged; Neoplasm Staging; Neoplastic Cells, Circulating; Portal Vein; Random Allocation | 2006 |
Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.
Recent advances in stem cell biology enable us to identify cancer stem cells in solid tumors as well as putative stem cells in normal solid organs. In this study, we applied side population (SP) cell analysis and sorting to established hepatocellular carcinoma (HCC) cell lines to detect subpopulations that function as cancer stem cells and to elucidate their roles in tumorigenesis. Among four cell lines analyzed, SP cells were detected in Huh7 (0.25%) and PLC/PRF/5 cells (0.80%), but not in HepG2 and Huh6 cells. SP cells demonstrated high proliferative potential and anti-apoptotic properties compared with those of non-SP cells. Immunocytochemistry examination showed that SP fractions contain a large number of cells presenting characteristics of both hepatocyte and cholangiocyte lineages. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) xenograft transplant experiments showed that only 1 x 10(3) SP cells were sufficient for tumor formation, whereas an injection of 1 x 10(6) non-SP cells did not initiate tumors. Re-analysis of SP cell-derived tumors showed that SP cells generated both SP and non-SP cells and tumor-initiating potential was maintained only in SP cells in serial transplantation. Microarray analysis discriminated a differential gene expression profile between SP and non-SP cells, and several so-called "stemness genes" were upregulated in SP cells in HCC cells. In conclusion, we propose that a minority population, detected as SP cells in HCC cells, possess extreme tumorigenic potential and provide heterogeneity to the cancer stem cell system characterized by distinct hierarchy. Topics: alpha-Fetoproteins; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Flow Cytometry; Gene Expression Regulation, Neoplastic; Hepatocytes; Humans; Immunohistochemistry; In Vitro Techniques; Keratins; Liver Neoplasms; Neoplasm Transplantation; Neoplastic Stem Cells; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Transplantation, Heterologous | 2006 |
Hepatoid carcinoma with serous component of the fallopian tube: a case report with immunohistochemical and ultrastructural studies.
A very rare case of hepatoid carcinoma with serous component arising in the fallopian tube of a 79-year-old woman is presented. The lesion was a 5.0-cm unencapsulated, yellowish-white soft mass. The tumor was composed of hepatoid carcinoma (90%) and serous carcinoma (10%) components. The hepatoid carcinoma was histologically characterized by a proliferation of round to polygonal cells arranged in a trabecular, tubular, sinusoidal, papillary, or solid pattern. The serous component in the fallopian tube also showed in situ lesions. Both components showed an infiltration into the surface of the left ovary, omentum, peritoneum including the pouch of the Douglas, and serosa of the colon. Immunohistochemically, the hepatoid carcinoma was positive for alpha-fetoprotein, polyclonal carcinoembryonic antigen (CEA), hepatocyte paraffin 1, albumin, epithelial membrane antigen, and cytokeratin (CAM5.2). Ultrastructurally, the cytoplasm contained abundant ribosomes, moderate amounts of mitochondria, and rough endoplasmic reticulum that developed into a meshwork and contained mitochondria within it. Microbile channel-like structures and desmosomes were occasionally observed. The association with serous carcinoma indicates mullerian origin rather than germ cell origin. The patient received chemotherapy and was alive without disease at 10 months after surgery. Topics: Aged; alpha-Fetoproteins; Carcinoma, Hepatocellular; Diagnosis, Differential; Fallopian Tube Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron, Transmission | 2006 |
The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin.
Cytokeratin (CK) 7 and CK19 expression, present in hepatic progenitor cells (HPCs) and in cholangiocytes but not in normal hepatocytes, has been reported in some hepatocellular carcinomas (HCCs); however, the incidence and relevance of this expression in HCC in Caucasians is not known. Therefore, our aim was to study the occurrence and clinicopathological characteristics of HCC expressing CK7 and/or CK19 in 109 Caucasian patients.. The expression of hepatocellular differentiation markers (Hepar, canalicular polyclonal carcinoembryonic antigen), biliary/progenitor cell markers (CK7, CK19), alpha-fetoprotein (AFP), p53 and beta-catenin in HCC was semiquantitatively assessed by immunohistochemistry. Of 109 HCCs, 78 were CK7-/CK19- (72%), 13 CK7+/CK19- (12%), seven CK7-/CK19+ (6%), 11 CK7+/CK19+ (10%). CK19 expression was significantly associated with elevated serum AFP (400 ng/ml) (P = 0.023), tumour AFP expression (P < 0.0001), presence in serum of anti-hepatitis B core (P = 0.016), less fibrosis in non-neoplastic parenchyma (P = 0.009) and less nuclear beta-catenin expression (P = 0.021). CK7 expression was significantly associated with elevated serum bilirubin (> 2 mg/dl) (P = 0.0005) and less nuclear beta-catenin expression (P = 0.003). HCC expressing CK19 had a higher rate of recurrence (P = 0.009, hazard ratio 12.5, n = 31) after liver transplantation compared with CK19- tumours.. In our series, 28% of HCCs contained cells expressing CK7 and/or CK19. They potentially derive from HPCs. The higher recurrence rate of CK19+ HCC after transplantation suggests a worse prognosis for these HCCs compared with CK19- HCC. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Stem Cells; White People | 2006 |
Primary hepatic carcinoid tumours: report of two cases.
Topics: Adult; Biomarkers; Biomarkers, Tumor; Carcinoid Tumor; Carcinoma, Hepatocellular; Chromogranin A; Cytoplasmic Granules; Diagnosis, Differential; Female; Hemangioma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Synaptophysin; Treatment Outcome | 2006 |
Gene expression associated with the decrease in malignant phenotype of human liver cancer cells following stimulation with a histone deacetylase inhibitor.
Sodium butyrate is a short-chain fatty acid produced by fermentation in the gastrointestinal tract. It induces differentiation of several kinds of cancer by inhibiting histone deacetylase activity. We have reported that butyrate stimulates hepatocellular carcinoma cells into their normal phenotype. Since sodium butyrate affects both differentiation and apoptosis, we investigated expression of bcl-2-related genes in a human hepatocellular carcinoma cell line HCC-T. The expression of anti-apoptotic Bcl-2 and Mcl-1/EAT was up-regulated 4 h after the treatment, while pro-apoptotic Bax expression did not change. Gene expressions in the early stage of butyrate-stimulation were investigated by the differential display assay and the cDNA expression array. Laminin and keratin 18 were increased 6 h after the stimulation with sodium butyrate. The results of cDNA expression array revealed up-regulation of cell cycle inhibitory genes such as cyclin-dependent kinase 4 inhibitor, and interferon-related genes such as STAT2 and 3, while down-regulation of cyclin-dependent kinase 2 and cyclin E. Up-regulated production of p21WAF-1 and Mcl-1/EAT was also confirmed by Western blotting. The cytoskeletal change indicated by up-regulation of laminin and keratin 18 may be an important factor in the decrease in malignant phenotype of cancer cells. Up-regulation of interferon-related genes indicated that butyrate-treatment might induce a similar phenotypic change to that induced by type 1 interferons. This study suggests several target genes for the future gene therapy of cancer or genes preventing cancer development from pre-malignant tissues. Topics: Antineoplastic Agents; Apoptosis; Butyrates; Carcinoma, Hepatocellular; CDC2-CDC28 Kinases; Cell Cycle Proteins; Cell Line, Tumor; Cyclin E; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p21; Down-Regulation; Enzyme Inhibitors; Gene Expression; Gene Expression Profiling; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Isobutyrates; Keratin-18; Keratins; Laminin; Liver Neoplasms; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-bcl-2; Up-Regulation | 2005 |
Apoptosis in chronic viral hepatitis parallels histological activity: an immunohistochemical investigation using anti-activated caspase-3 and M30 cytodeath antibody.
Apoptosis is implicated as a major pathogenic mechanism in chronic hepatitis B and C. Previous studies of the relationship between apoptotic rates and histological necroinflammatory activity have produced conflicting results. Hepatocyte apoptosis was assessed in liver tissue from 32 cases of chronic viral hepatitis, seven cases of hepatocellular carcinoma (HCC) and six cases of steatohepatitis as non-viral disease controls and eight cases of control liver. Apoptotic rates were measured using H&E morphological assessment and immunohistochemical staining with antibodies to activated caspase-3 and M30. Histological necroinflammatory activity of viral hepatitis cases was scored using the Knodell scoring system, and the cases were divided according to their score into group 1 (mean 2.43 +/- 0.48) and group 2 (mean 7.80 +/- 0.49). Apoptotic indices were significantly higher in group 2 than group 1 using H&E (11.53 +/- 2.70 vs. 0 +/- 0, P=0.015) and activated caspase-3 (22.01 +/- 5.27 vs. 1.79 +/- 1.79, P=0.03) methods but were not significantly higher with M30 (3.80 +/- 1.74 vs. 0 +/- 0, P=0.207). Apoptotic scores using an antibody to activated caspase-3 are significantly higher in cases of chronic viral hepatitis with greater histological necroinflammatory scores, supporting a central role for apoptosis in disease pathogenesis. This method offers an alternative to routine histological assessment for measuring disease activity. Topics: Antibodies, Monoclonal; Apoptosis; Carcinoma, Hepatocellular; Caspase 3; Caspases; Fatty Liver; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Retrospective Studies | 2005 |
Proteomic profiling of cellular proteins interacting with the hepatitis C virus core protein.
Hepatitis C virus (HCV) is a causative agent of chronic hepatitis and hepatocellular carcinoma. The core protein of HCV packages the viral RNA genome to form a nucleocapsid. In addition to its function as a structural protein, core protein is involved in regulation of cellular transcription, virus-induced transformation, and pathogenesis. To gain insights into cellular functions of the core protein by identification of cellular proteins interacting with the core protein, we employed a proteomic approach. Hepatocytes soluble cytoplasmic proteins were applied to the core proteins immobilized on Ni-nitrilotriacetic resin and total bound cellular proteins were resolved by 2-DE. Analyses of interacting proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry allowed identification of 14 cellular proteins binding to the core protein. These proteins include DEAD-box polypeptide 5, similar in function to a known protein identified previously by yeast two-hybrid screening and 13 newly identified cellular proteins. Interestingly, nine protein spots were identified as intermediate microfilament proteins, including cytokeratins (five spots for cytokeratin 8, two for cytokeratin 19, and one for cytokeratin 18) and vimentin. Cytokeratin 8 and vimentin, which were previously shown to be involved in the infection processes of other viruses, were further analyzed to confirm their in vivo interactions with the core protein by immunoblotting and immunofluorescence microscopy. We discuss the functional implications of the interactions of the core protein with newly identified cellular proteins in HCV infection and pathogenesis. Topics: Animals; Blotting, Western; Carcinoma, Hepatocellular; Cattle; Cell Culture Techniques; Cell Line, Tumor; Cytoplasm; Electrophoresis, Gel, Two-Dimensional; Hepacivirus; Hepatocytes; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Mass Spectrometry; Nickel; Nitrilotriacetic Acid; Precipitin Tests; Proteins; Proteomics; Recombinant Proteins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Trypsin; Vimentin; Viral Core Proteins | 2005 |
Small-cell tumors of the liver: a cytological study of 91 cases and a review of the literature.
This study was designed to consider the cytomorphological spectrum, differential diagnosis, and the role of ancillary studies in small-cell tumors of the liver. Three independent pathologists reviewed cytological slides from 91 cases of small-cell tumors of the liver. The results were compared with the findings of three recently published studies (Cytopathology 11 (2000) 262-267; Diagn Cytopathol 19 (1998) 29-32; and Acta Cytol 40 (1996) 937-947). The role of immunohistochemistry in reaching timely and specific diagnoses was also examined. The diagnostic categories included 44 cases of metastatic small-cell undifferentiated carcinoma, 15 cases of metastatic neuroendocrine carcinoma, 10 cases of metastatic adenocarcinoma, 7 cases of malignant lymphoma, 4 cases of hepatocellular carcinoma with small-cell features, 2 cases of cholangiocarcinoma, 1 case of poorly differentiated carcinoma, and 8 cases of rare tumors including granulosa cell tumor (2 cases), sarcoma (4 cases), malignant melanoma with small-cell features (1 case), and meningioma with small-cell features (1 case). Metastatic granulosa cell-tumor, metastatic melanoma, and metastatic meningioma should be included in the differential diagnoses of small-cell malignancies found in the liver. Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Carcinoma, Hepatocellular; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Cholangiocarcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Lymphoma; Male; Middle Aged; Mucin-1; Review Literature as Topic; S100 Proteins; Vimentin | 2005 |
Primary liver carcinoma arising in people younger than 30 years.
Primary liver carcinomas in children and young adults are uncommon and poorly described. We examined primary liver carcinomas in people younger than 30 years and performed immunostains for markers of biliary (cytokeratin [CK] 7, CK19, CD56) and hepatocellular (HepPar) differentiation. We found 23 primary liver carcinomas were found: 13 hepatocellular carcinomas (HCCs), 9 fibrolamellar carcinomas (FLCs), and 1 cholangiocarcinoma. Most HCCs showed compact (n = 7) or trabecular (n = 4) growth patterns. The Edmondson grades were as follows: 1, 3 tumors; 2, 8 tumors; and 3, 2 tumors). All HCCs and FLCs were HepPar(+). All FLCs and 7 of 9 HCCs were CK7(+). In contrast, a control group of 65 adult HCCs showed less CK7 positivity (24 [37%]; P = .03). CK19 was positive in 2 HCCs and CD56 in 1 HCC. No chronic background liver disease was seen, although 3 cases showed foci of altered hepatocytes. HCCs are the most common primary liver carcinoma in children and young adults followed by FLCs. They are morphologically similar to adult HCC, but more likely to be CK7(+). Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Animals; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; CD56 Antigen; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver Neoplasms; Male; Middle Aged; Retrospective Studies | 2005 |
Immunohistochemical analysis in hepatocellular carcinoma: does age matter?
Topics: Adolescent; Age Factors; Aged; Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Child; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver Neoplasms; Middle Aged | 2005 |
'Scirrhous' type hepatocellular carcinomas: a special reference to expression of cytokeratin 7 and hepatocyte paraffin 1.
'Scirrhous' hepatocellular carcinoma (scirrhous HCC) is extremely rare and its characteristics remain unclear. We investigated the clinicopathological and immunohistochemical features of scirrhous HCC, compared with those of ordinary hepatocellular carcinoma (ordinary HCC).. We compared the clinicopathological and immunohistochemical features of 20 resected cases of scirrhous HCC with those of 69 resected cases of ordinary HCC. Scirrhous HCC was characterized by its gross and histological findings, such as a higher proportion of contiguous multinodular type tumours, the absence of a complete fibrous capsule around the tumour, the absence of tumour necrosis and highly preserved portal tracts in the tumour. The immunohistochemical results revealed a significantly higher expression of cytokeratin 7 and a significantly lower expression of hepatocyte paraffin 1 in scirrhous HCC than in ordinary HCC (P<0.0001, respectively). There were no significant differences in proliferative activity and survival curves between the patients with scirrhous HCC and those with ordinary HCC.. Scirrhous HCC has several particular gross, histological and immunohistochemical features. In particular, we would like to emphasize the greater immunohistochemical expression of cytokeratin 7 and lower expression of hepatocyte paraffin 1 in scirrhous HCC than in ordinary HCC. Topics: Adenocarcinoma, Scirrhous; Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Diagnosis, Differential; Female; Hepatocytes; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver Neoplasms; Male; Middle Aged; Prognosis | 2005 |
[A particular hepatocellular carcinoma combining the ordinary and the fibrolamellar variant].
Fibrolamellar carcinoma (FLC) of the liver is a rare variant of hepatocellular carcinoma (HCC) occurring on non cirrhotic liver. Since its first description by Hugh Edmondson in 1956, 200 cases of FLC have been reported in the literature, but only some cases describe the association of the ordinary HCC with the FLC within the same lesion. We report in this study the case of a 14-year-old female patient with a hepatic mass whose radiological aspect evoked a nodular and focal hyperplasia. Histologically, this tumor was composed of area of FLC mixed with ordinary HCC. Staining for cytokeratine 7 was positive in the FL component and negative in the ordinary HCC component. Topics: Adolescent; Carcinoma, Hepatocellular; Female; Humans; Keratin-7; Keratins; Liver Neoplasms | 2005 |
Diagnostic significance of aquaporin-1 in liver tumors.
The diagnostic utility of aquaporin (AQP)-1 in liver tumors was tested and compared with other well-established markers. In 30 cholangiocarcinomas (CCs), 20 hepatocellular carcinomas (HCCs), and 10 metastatic colorectal carcinomas (MCCs) of the liver, expression of AQP-1, CD10, cytokeratin (CK) 7, CK20, and polyclonal carcinoembryonic antigen (pCEA) was tested. In addition, staining patterns of CD10 and pCEA were analyzed. To compare the selectivity of AQP-1 and CK7 as possible markers for differentiated cholangiocytes, liver biopsies of cholestatic disease were also analyzed. Aquaporin-1 expression was found in 93% of all CCs compared with 0% of HCC (P < .000001) and with 30% of MCC (P < .01). CD10 was positive in 16.7% of CC compared with 40% of HCC (P < .04) and to 20% of MCC (not significant). Cytokeratin 7 was positive in 90% of CC compared with 10% of HCC (P < .00001) and with 20% of MCC (P < .0001). Cytokeratin 20 was positive in 90% of MCC compared with 16.7% of CC (P < .0001) and with 20% of HCC (P < .00001). Canalicular staining patterns of CD10 and pCEA were observed in HCC (100% and 89.5%, respectively) but typically not in CC (0% and 6.7%, respectively) and never in MCC. In cholestatic disease, AQP-1 was expressed in differentiated epithelial cells of the bile ducts, whereas CK7-positive hepatocytes of Rappaport zone 1 did not show any AQP-1 reactivity. Therefore, AQP-1 seems to be a highly selective marker for differentiated cholangiocytes and can be very helpful in the differential diagnosis of liver tumors. Topics: Adult; Aged; Aged, 80 and over; Aquaporin 1; Biomarkers, Tumor; Capillaries; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholangiocarcinoma; Cholestasis; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver Neoplasms; Male; Middle Aged; Neprilysin | 2005 |
Cellular and stromal characteristics in the scirrhous hepatocellular carcinoma: comparison with hepatocellular carcinomas and intrahepatic cholangiocarcinomas.
Scirrhous hepatocellular carcinoma (SHCC) is a rare variation of HCC, for which characteristics of tumor cells and the fibrotic stroma have not been clarified in detail. The present study was therefore carried out to elucidate cytological features of tumor and stromal cells and components of the stromal extracellular matrix in 15 SHCC patients undergoing hepatectomy without preoperative transarterial embolization. Diagnosis was on the basis of a scirrhous histological pattern exceeding 50% of the tumor area. Expression of cytoplasmic and extracellular matrix proteins was compared among SHCC, HCC and intrahepatic cholangiocarcinoma (ICC) cases with immunohistochemical staining. The lesions could be histologically divided into radiating and sinusoidal types. Common stromal components of SHCC and ICC were collagen types I and III. There was no expression of laminin-5 in the stroma of SHCC, but it was present in almost all ICC cases. Tenascin-C expression was significantly lower in the SHCC cases and its distribution differed between SHCC and ICC. Matrix metalloproteinase-7 (MMP-7) expression was significantly higher in SHCC compared with HCC. Almost all stromal cells were alpha-smooth muscle actin-positive both in SHCC and ICC, whereas glial fibrillary acid protein (GFAP)-positive stromal cells were significantly more increased in ICC than in SHCC. SHCC clearly differed from HCC with respect to collagen types I, III and MMP-7 expression, and from ICC with regard to stromal components including laminin-5, tenascin-C and GFAP(+) stromal cells. Topics: Adenocarcinoma, Scirrhous; Aged; Apoptosis; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cell Proliferation; Cholangiocarcinoma; Collagen Type I; Collagen Type III; Female; Fibroblast Growth Factor 2; Humans; Keratins; Laminin; Liver Neoplasms; Male; Matrix Metalloproteinase 7; Middle Aged; Tenascin | 2005 |
Hepatocellular carcinoma with mesothelioma-like dissemination.
Reported herein is a case of hepatocellular carcinoma (HCC) with unusual peritoneal dissemination masquerading as peritoneal mesothelioma. A 61-year-old man was clinically found to have multiple tumors in his abdominal cavity; peritonitis carcinomatosa was suspected. An autopsy revealed numerous tumors of various sizes in the abdominal serosa, omentum, and diaphragm. No signs of tumor, fibrosis, or cirrhosis were found in the liver, except for a small nodule in the hepatic triangular ligament. Histologically, the tumor cells proliferated in thick trabeculae or in sheets and formed a few canaliculi and tubules with homogenously brown contents in their lumina, which stained positively with Hall stain. Immunohistochemically, these tumors were positive for hepatocyte, alpha-fetoprotein (AFP) and low-molecular-weight cytokeratin; were focally positive for pan-cytokeratin and epithelial membrane antigen (EMA); and were negative for high-molecular-weight cytokeratin, vimentin, and calretinin. Carcinoembryonic antigen (CEA) produced a bile canalicular immunohistochemical staining pattern. Thus, the tumor was diagnosed as an HCC (Edmondson II type) of the triangular ligament with massive peritoneal dissemination. The origin of this tumor and its differential diagnosis (malignant mesothelioma, hepatoid adenocarcinoma, and hepatoid yolk sac tumor) are discussed. Topics: Adenocarcinoma; alpha-Fetoproteins; Calbindin 2; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Mesothelioma; Middle Aged; Mucin-1; Peritoneal Neoplasms; S100 Calcium Binding Protein G; Vimentin | 2005 |
Hepatoid adenocarcinoma of the gallbladder.
Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholecystectomy; Endosonography; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Liver; Lymph Node Excision; Neprilysin; Treatment Outcome | 2005 |
Immunohistologic attempt to find carcinogenesis from hepatic progenitor cell in hepatocellular carcinoma.
To clarify whether hepatocellular carcinoma (HCC) originates from hepatic progenitor cells and whether there is any correlation with the clinicopathologic factors of HCC, we reviewed 217 resected HCC specimens.. Immunohistochemical examination of cytokeratin (CK) 7, CK19, CD34, and CD117 (c-KIT) was performed. Overexpression of CK7 and CK19 indicates differentiation from cholangiocellular and hepatic progenitor cells, while overexpression of CD34 and CD117 indicates hepatic stem cells. Fresh specimens were obtained from 20 HCC patients for mutation of the c-KIT gene.. CK7, CK19, and CD117 were positive in 41, 9.7, and 0.9% of the HCC specimens, respectively, and CD34 was never positive. None of the fresh HCC specimens demonstrated a c-KIT mutation. CK19 positivity was significantly correlated with a positive hepatitis B core antibody, and with poor survival outcome, and tended to correlate with poor histologic differentiation.. These results suggest that: (i) about 10% of HCCs with typical histologic features originate from an intermediate hepatic progenitor cell, such as the canal of Hering and oval cells in the rat, or acquire the characteristics of cholangiocellular epithelium by metaplasia; (ii) HCC with typical histologic features rarely originates from hepatic stem cells, and (iii) patients with CK19-positive HCC have a poor prognosis. Topics: Analysis of Variance; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Chi-Square Distribution; Female; Hepatocytes; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Prognosis; Risk Factors; Statistics, Nonparametric; Stem Cells; Survival Rate | 2005 |
From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis.
To better understand the mechanism underlying the hepatocellular carcinoma (HCC) metastasis and to search potential markers for HCC prognosis, differential proteomic analysis on two well-established HCC cell strains with high and low metastatic potentials, MHCC97-H and MHCC97-L, was conducted using two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/time-of-flight mass spectrometry. Cytokeratin 19 (CK19) was identified and found to be overexpressed in MHCC97-H as compared with MHCC97-L. This result was further confirmed by two-dimensional Western blot analysis and immunofluorescence assay. Furthermore, one-dimensional Western blot analysis showed consistently increased CK19 expression in progressively more metastatic cells. Immunohistochemical study on 102 human HCC specimens revealed that more patients in the CK19-positive group had overt intrahepatic metastases (satellite nodules, p < 0.05; vascular tumor emboli, p < 0.001; tumor node metastatis staging, p < 0.001). CK19 fragment CYFRA 21-1 levels measured in sera from nude mice model of human HCC metastasis with radioimmunoassay increased in parallel with tumor progression and rose remarkably when pulmonary metastases occurred. The results demonstrated that overexpression of CK19 in HCC cells is related to metastatic behavior. Serum CK19 level might reflect the pathological progression in some HCC and may be a useful marker for predicting tumor metastasis and a therapeutic target for the treatment of HCC patients with metastases. Topics: Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Line, Tumor; Electrophoresis, Gel, Two-Dimensional; Humans; Keratins; Liver Neoplasms; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Metastasis; Peptide Fragments; Proteome; Random Allocation; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization | 2004 |
Sarcomatoid hepatocellular carcinoma with hepatoblastoma-like features in an adult.
A mixed epithelial and mesenchymal tumor of the liver arising in an adult is rare and is mostly classified as sarcomatoid hepatocellular carcinoma (HCC). In this study, a case of sarcomatoid HCC in an adult with hepatoblastoma (HB)-like features, which produced difficulty in the differential diagnosis between sarcomatoid HCC and mixed HB, is presented. The epithelial component of the tumor composed of poorly differentiated HCC, Edmondson's grade III, and more primitive components, which were embryonal and small cell undifferentiated components of HB-like areas. The small undifferentiated cells surrounded HCC and the embryonal component of HB-like area, and revealed transition partly to areas of rhabdomyosarcoma. A small portion of chondrosarcoma was also noted. Immunohistochemical analysis showed that HCC and the embryonal component of HB-like areas expressed alpha-fetoprotein (AFP) and cytokeratin 8. The small undifferentiated cells were negative for AFP but stained with cytokeratin 8 as well as CD56, which is a marker of primitive cells in many sarcoma and HB. It is not certain whether small undifferentiated cells belong to hepatic progenitor cells or primitive mesenchymal cells. Polymerase chain reaction-single-strand conformation polymorphism analysis for beta-catenin mutation using microdissection revealed no mutation of any components. A review was undertaken of the cases previously reported as adult hepatoblastoma without detailed immunohistochemical study and consider many of them may be sarcomatoid HCC. These primitive and sarcomatoid components would be arising from the dedifferentiation process of HCC. Topics: Aged; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; CD56 Antigen; Diagnosis, Differential; Fatal Outcome; Hepatoblastoma; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Neoplasms, Complex and Mixed; Sarcoma; Tomography, X-Ray Computed | 2004 |
Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics.
To establish a "stepwise metastatic human hepatocellular carcinoma (HCC) cell model system" for in-depth study of the underlying mechanisms of HCC metastasis.. Using MHCC97- a metastatic human hepatocellular carcinoma (HCC) cell line reported in 1999-as the parent cells, we subsequently established three cell lines (MHCC97-L, HMCC97-H, and HCCLM3) with increasing spontaneous metastatic potential. Now, the fourth cell line with unique multiple metastatic characteristics has been established by six rounds of in vivo selection.. This cell line, designated as HCCLM6, is a polygonal epithelial cell with hypotriploid karyotype, the modal chromosomes are 55-58, and marker chromosomal abnormalities include i(1) (q10), i(8)(q10), der (4) t(4;8)(q31;q22), i(X)(q10). The cell population doubling time was 32 h. Fluorescent PCR showed HBV DNA integration in the cellular genome. Thirty-five days after HCCLM6 was injected subcutaneously into BALB/c nude mice, prominent lung metastases occurred in 100% of the recipient animals. When tumor tissue was orthotopically implanted into the liver of nude mouse, widespread loco-regional and pulmonary metastases occurred. Inoculation of this cell into the footpad of nude mice also produced 75% regional lymph node metastasis. Compared with MHCC97-L which was not metastastatic via subcutaneous or footpad inoculation and 40% metastatic via orthotopic inoculation, HCCLM6 had increased expression of matrix metalloproteinase (MMP-2 and MMP-9) and cytokeratin 19 (CK19), and decreased expression of Rb2/p130. The establishment of this new cell line has completed our stepwise metastatic HCC cell mode system, which was characterized by a similar genetic background but with significant differences in spontaneous metastasis behavior.. The study supports the theory that cancer metastasis is a highly selective dynamic process and the cell model system could be a useful platform for the study of HCC metastasis. Topics: Animals; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Chromosome Aberrations; DNA, Viral; Gene Expression Regulation, Neoplastic; Hepatitis B virus; Humans; Karyotyping; Keratins; Liver Neoplasms; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Mice, Nude; Proteins; Retinoblastoma-Like Protein p130; Reverse Transcriptase Polymerase Chain Reaction | 2004 |
A novel diagnostic marker, p28GANK distinguishes hepatocellular carcinoma from potential mimics.
To investigate the sensitivity, specificity, and spatial distribution of the product of p28 gene (p28(GANK) protein) in human hepatocellular carcinoma (HCC) and nonhepatocellular carcinomas in relation to immunostaining with Cytokeratin 18 (CK18), alpha-fetoprotein (AFP), and Hepatocyte paraffin 1 (HepPar1).. In this retrospective study, formalin-fixed paraffin-embedded tissues from 24 HCCs, five intrahepatic cholangiocarcinomas (ICC), five combined hepatocellular cholangiocarcinomas (C-HCC-CC) and mine metastatic hepatic carcinomas (MHC) were immunostained for p28(GANK) as well as CK18, AFP and HepPar1. Only cases with more intensified staining in carcinoma contrast to the adjacent liver tissues were accepted as positive.. In HCC, p28(GANK) was expressed restrictively in hepatocytes of both para-lesion and carcinoma liver tissues, while absent in the bile duct epithelial cells, Kupffer cells, and other interstitial cells. The positive staining of p28(GANK) was noted in 16 (66.7%) specimens of HCC and three (60.0%) specimens of C-HCC-CC, and no specific lesion staining was found in all tested specimens of ICC and MHC. Sensitivity and specificity for hepatocyte-originated carcinoma were, respectively, 65.5% and 100% for p28(GANK), 79.3% and 85.2% for CK18, 20.7% and 100% for AFP, 79.3% and 92.0% for HepPar1.. The hepatocytic staining for p28(GANK) is clearly useful in differentiating hepatocyte-originated carcinoma from non-HCC. p28(GANK) may be used as an ancillary marker for the diagnosis of HCC. Topics: alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Hepatocytes; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Oncogene Proteins; Paraffin; Proteasome Endopeptidase Complex; Proto-Oncogene Proteins; Sensitivity and Specificity | 2004 |
Immunohistochemical profiles of Mallory body by a panel of anti-cytokeratin antibodies.
Mallory bodies (MBs) are hyaline inclusions found in a variety of liver diseases. Because the major components of MBs are cytokeratins (CKs), CK profiles of MBs were examined immunohistochemically in 37 autopsied liver specimens (including a variety of nontumor pathological livers and hepatocellular carcinomas), using 13 antibodies against specific CKs: 34betaB4 (CK 1), OV-TL12/30 (CK 7), 34betaH11 (CK 8), LHP1 (CK 10), KS-1A3 (CK 13), LL002 (CK 14), LHK15 (CK 15), LL025 (CK 16), E3 (CK 17), DC10 (CK 18), b170 (CK 19), Ks20.8 (CK 20), and 34betaE12 (CKs 1, 5, 10, and 11). Positive staining rates of MBs in 37 cases were as follows: CK 8, 100% (37/37); CK 18, 100% (37/37); CK 19, 57% (21/37). CK 7, 49% (18/37); CK 20, 35% (13/37); CK 1, CK 5, CK 10, CK 11, CK 13, CK 14, CK 15, CK 16, and CK 17 were all negative in MBs. CK expression patterns in MBs found in tumor or non-tumor hepatocytes was basically similar. Thus, all present MBs were composed of similar material with common antigenic determinants, regardless of underlying disease; in particular, they consistently contained CK 8 and CK 18, and frequently contained CK 7, CK 19, and CK 20. Topics: Carcinoma, Hepatocellular; Hepatocytes; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Liver Diseases; Liver Neoplasms | 2004 |
[Study on the relationship between serum cytokeratin 19 level in hepatocellular carcinoma patients and the clinico-pathologic characteristics].
As our previous comparative proteomics study on high and low metastasis human hepatocellular carcinoma (HCC) cell strains revealed that cytokeratin 19 (CK19) was related to higher metastasis potential, we further investigated the relationship between serum CK19 level in HCC patients and their clinico-pathologic characteristics.. Serum CK19 levels of 101 normal controls and 108 pathology-proven HCC patients were determined using radioimmunoassay, and the their correlation with clinico-pathologic parameters were studied.. The upper limit of one-side 98% confidence interval of normal serum CK19 level was 2.3 microg/L. Among 108 HCC patients, 24 (22.2%) had increased serum CK19 level, ranging from 2.4 to 45.5 microg/L. There were 12 patients (11.1%) with increased CK19 level but normal AFP level. The percentage of poor differentiated tumor was higher in CK19 increased cases (37.5%, 9/24) than in CK19 normal cases (20.2%, 17/84). Moreover, the presence of portal vein tumor emboli was significantly higher in CK19 increased cases (25.0%, 6/24) than in CK19 normal cases (6.0%, 5/84). (Chi-square = 7.403, P < 0.01) In addition, the percentage of TNM stage III/IV tumor was significantly higher in CK19 increased patients (54.2%, 13/24) than in CK19 normal cases. (chi-square = 13.300, P < 0.005). Some HCC patients do have increased serum CK19 level, which could be related to portal vein tumor emboli, poor tumor differentiation and advanced tumor stages. Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Humans; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Proteins; Peptide Fragments; Proteome | 2004 |
Effects of diode 808 nm GaAlAs low-power laser irradiation on inhibition of the proliferation of human hepatoma cells in vitro and their possible mechanism.
Low-power laser irradiation (LPLI) has come into a wide range of use in medical field. Considering basic research, LPLI can enhance DNA synthesis and increases proliferation rate of human cells. But only a few data about the effects of LPLI on human liver or hepatoma cells are available. The cytoskeleton plays important roles in cell function and therefore is implicated in the pathogenesis of many human liver diseases, including malignant tumors. In our previous study, we found the stability of cytokeratin molecules in human hepatocytes was related to the intact microtubule network that was influenced by colchicine. In this study, we are going to search the effect of LPLI on proliferation of human hepatoma cell line HepG2 and J-5 cells. In addition, the stability of cytokeratin and synemin (one of the intermediate filament-associated proteins) were analyzed under the action of LPLI to evaluate the possible mechanism of LPLI effects on proliferation of human hepatoma cells. In experiment, HepG2 and J-5 cells were cultured in 24-well plate for 24 hours. After irradiation by 130 mW diode 808 nm GaAlAs continue wave laser in different time intervals, the cell numbers were counted. Western blot and immunofluorescent staining examined the expression and distribution of PCNA, cytokeratin and synemin. The cell number counting and PCNA expression were evaluated to determine the proliferation. The organization and expression of cytokeratin and synemin were studied to identify the stability of cytoskeleton affected by LPLI. The results revealed that proliferation of HepG2 and J-5 cells was inhibited by LPLI since the cell number and PCNA expression was reduced. Maximal effect was achieved with 90 and 120 seconds of exposure time (of energy density 5.85 J/cm2 and 7.8 J/cm2, respectively) for HepG2 and J-5, respectively. The decreased ratio of cell number by this dose of irradiation was 72% and 66% in HepG2 and J-5 cells, respectively. Besides that, the architecture of intermediate filaments in these cells was disorganized by laser irradiation. The expression of intermediate filament-associated protein, synemin, was also reduced. Two significant findings are raised in this study: (1) Diode 808 nm GaAlAs continuous wave laser has an inhibitory effect on the proliferation of human hepatoma cells line HepG2 and J-5. (2) The mechanism of inhibition might be due to down-regulation of synemin expression and alteration of cytokeratin organization that was caused by laser irr Topics: Analysis of Variance; Blotting, Western; Carcinoma, Hepatocellular; Cell Count; Cell Line, Tumor; Cell Proliferation; Fluorescein-5-isothiocyanate; Fluorescent Antibody Technique, Indirect; Fluorescent Dyes; Humans; In Vitro Techniques; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Low-Level Light Therapy; Phalloidine; Proliferating Cell Nuclear Antigen; Radiation Dosage; Time Factors | 2004 |
Small epithelial cells in human liver cirrhosis exhibit features of hepatic stem-like cells: immunohistochemical, electron microscopic and immunoelectron microscopic findings.
To investigate whether cells with features similar to those of the oval cells of rodents and the small epithelial cells (SEC) recently described in certain human liver diseases, i.e. hepatic progenitor cells, also occur in human liver cirrhosis.. Surgical specimens from 35 cases of hepatitis B virus-positive cirrhosis (30 cases containing hepatocellular carcinoma) were investigated by immunohistochemical staining for cytokeratin 7 and albumin. Electron microscopic investigations, and immunoelectron microscopic investigations using the same antibodies and a double-labelling technique were performed in 15 and seven cases, respectively. SEC were observed in proliferated bile ductules, at the margins of regenerating nodules and in the fibrous septa in all cases of cirrhosis. The SEC were morphologically similar to the SEC described previously, and to the oval cells seen in experimental hepatocarcinogenesis. They were characterized by their small size, oval shape, scanty electron-dense or electron-lucent cytoplasm, a high nucleo-cytoplasmic ratio, tonofilaments and intercellular junctions. Immunoelectron microscopy revealed that the SEC co-expressed cytokeratin 7 and albumin. Both relatively undifferentiated SEC and SEC with morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes were found.. SEC that exhibit morphological and immunophenotypical features of the SEC seen in certain other liver diseases are found in cirrhosis. These findings further support the hypothesis that a bipotent hepatic stem cell that may give rise to biliary epithelial cells and hepatocytes exists in the human liver. Topics: Albumins; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Fluorescent Antibody Technique, Indirect; Hepatitis B; Hepatocytes; Humans; Keratin-7; Keratins; Liver Cirrhosis; Liver Neoplasms; Microscopy, Immunoelectron; Stem Cells | 2003 |
Combined hepatocellular and cholangiocarcinoma with marked squamous cell carcinoma components arising in non-cirrhotic liver.
We report a surgical case of liver tumor, 40 x 35 mm in size, with squamous cell carcinoma (SCC) and hepatocellular carcinoma (HCC) components in a 60-year-old Japanese man with steatohepatitis. Most of the SCC component showed typical intercellular bridge and keratinization, while most of the HCC components showed a thick trabecular pattern with mild to moderate nuclear atypia. Both components transit each other without undifferentiated foci; however, a small foci showing glandular structure was intermediated. No cyst formation was found in the liver. The primary site of the squamous cell carcinoma was not detected in general clinical and radiological examination. Immunohistochemical analysis revealed that part of the HCC components neighboring the SCC showed patchy and weak expression of cytokeratin 7. There are several possibilities for the origin of squamous cell carcinoma in this case: marked squamous metaplastic change of cholangiocarcinoma and/or HCC, and carcinoma originating from pleuripotential stem cells. Irregular fatty changes, scattered giant mitochondria and acellular fibrosis with bridging were seen in the liver; however, this patient had no episode of hepatitis-associated viral infection. This is an interesting case of combined hepatocellular and cholangiocarcinoma with marked SCC components arising in a non-cirrhotic fibrotic liver. Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Cholangiocarcinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Neoplasms, Multiple Primary; Stem Cells | 2003 |
Sarcomatous cholangiocarcinoma.
Topics: Adenocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Sarcoma; Vimentin | 2003 |
Laminin induces the expression of cytokeratin 19 in hepatocellular carcinoma cells growing in culture.
To study the abnormal cytokeratin (CK) expression, emergence of CK19 with or without CK7, in liver parenchymal cells and the role of laminin (LN), a basement membrane protein, in this process.. Six hepatocellular carcinoma (HCC) cell lines were examined for different CKs, LN and its receptor by immunocytochemistry and Western blotting. Double immunofluorescent reaction, laser-scanning confocal microscopy and an in vitro induction procedure were used to demonstrate the role of LN in regulating CK19 expression in these cells.. Immunoreactivities for CK8, CK18, CK7 and the receptor for LN were observed in all the six HCC cell lines examined. However, CK19 was merely found in four of the six cell lines, and was in any case associated with LN expression. Laser-scanning confocal microscopy demonstrated the concomitant presence of these two molecules in most of the positive cells. In the two HCC cell lines, originally negative for CK19, addition of LN to the culture medium resulted in an induction of CK19 in a dose-dependent manner. Both the artificially induced and the intrinsic production of CK19 were completely blocked by an antibody to LN.. LN can induce expression of CK19 in HCC cells in vitro, providing direct evidence for our hypothesis that the abnormal hepatocytic CK19 expression in situ is due to pathologic LN deposition. Topics: Carcinoma, Hepatocellular; Humans; Immunohistochemistry; Keratin-7; Keratins; Laminin; Liver Neoplasms; Receptors, Laminin; Tumor Cells, Cultured | 2003 |
Cytokeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver cancer.
Using an electrochemiluminescence immunoassay, CYFRA 21-1 concentrations were measured in sera from 187 patients with primary liver cancer (164 with hepatocellular carcinoma (HCC) and 23 with intrahepatic cholangiocarcinoma (ICC)) and 87 patients with benign liver diseases. Concentrations of CYFRA 21-1 were significantly higher in patients with ICC (5.0; interquartile range 3.1-10.7 ng ml(-1)) than in those with benign liver disease (1.4; 1.0-1.9; Mann-Whitney U-test, P<0.0001) or HCC (1.7; 1.1-2.7; Mann-Whitney U-test, P<0.0001). Using cutoff values selected for 95% specificity in the benign group (3.0 ng ml(-1)), CYFRA 21-1 showed higher sensitivity for ICC (87.0%) than three commonly used markers including alpha-fetoprotein (17.4%), carcinoembryonic antigen (34.8%), and carbohydrate antigen 19-9 (60.9%). Serum CYFRA 21-1 increased in ICC from stages I/II to IV (Kruskal-Wallis test, P=0.0102). CYFRA 21-1 concentration increased with extent of local invasion, but not nodal status. Serum CYFRA 21-1 represents a useful diagnostic test for ICC that offers high sensitivity. CYFRA 21-1 reflected differences in tumour burden, suggesting applicability to staging and follow-up. Topics: Adult; Aged; alpha-Fetoproteins; Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholangiocarcinoma; Humans; Keratin-19; Keratins; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Sensitivity and Specificity | 2003 |
Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence.
Clinicopathologic features and postoperative outcomes were investigated for patients who underwent curative surgery for biliary marker (CK7 and CK19)-positive hepatocellular carcinoma (HCC). Of 157 HCCs, 93 were CK7(-)CK19(-), 49 were CK7(+)-CK19(-), 1 was CK7(-)CK19(+), and 14 were CK7(+)- CK19(+). Semiquantitative analysis of expression levels demonstrated a significant correlation between CK7 and CK19 expression. Of various clinicopathologic parameters, tumor differentiation exhibited a significant correlation with CK7 and CK19 expression. All 15 patients with CK19-positive HCC also had anti-HBc. Log-rank test revealed that CK7 expression, CK19 expression, high aspartate aminotransferase (AST) activity, low albumin concentration, portal invasion, intrahepatic metastasis, and severe fibrosis (cirrhosis) reduced the tumor-free survival rate. Multivariate analysis demonstrated that CK19 expression, intrahepatic metastasis, and severe fibrosis were independent predictors of postoperative recurrence, while CK7 expression was not. Twelve of 15 patients with CK19-positive HCC had tumor recurrence within 2 years after surgery, a significantly higher incidence of early recurrence than for CK19-negative HCC. The incidence of extrahepatic disease, especially lymph node metastasis, was significantly higher for patients with CK19-positive HCC. These findings indicate that CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Survival Rate; Treatment Outcome | 2003 |
CYFRA 21-1 is released in TNF-alpha-induced apoptosis in the hepatocellular carcinoma cell line HuH-7.
Many types of cancer cells widely express cytokeratin 19 (CK19). Clinical investigations have suggested that serum CYFRA 21-1, a fragment of CK19, is one of the most useful tumor markers. In the present study, we hypothesized that released CYFRA 21-1 is closely associated with cellular apoptosis during tumor growth. Apoptosis was induced by tumor necrosis factor-alpha (TNF-alpha) in the HuH-7 hepatocellular carcinoma cell line. Both TNF-alpha-treated and non-treated cells of HuH-7 were simultaneously examined by immunoradiometric assay, annexin-V apoptosis analysis, immunohistochemical staining and colorimetric protease measurement. Levels of CYFRA 21-1 increased significantly in TNF-alpha-treated cells displaying a high percentage of apoptosis, granular-like aggregation of CK19, and elevated activity of caspase-3 in contrast to non-treated cells. Levels of CYFRA 21-1 decreased significantly after caspase-3 was inhibited in TNF-alpha-treated cells. Thus, the release of CYFRA 21-1 may suggest cellular apoptosis in the process of tumor growth. Topics: Antigens, Neoplasm; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Blotting, Western; Carcinoma, Hepatocellular; Caspase 3; Caspases; Culture Media; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha | 2002 |
Adult-type hepatocellular carcinoma in the center of a fibrolamellar hepatocellular carcinoma.
A large hepatic tumor was detected in the noncirrhotic liver of a 27-year-old female patient. The tumor was radiologically characterized by a peripheral mass encircling a central ovoid tumor, and was resected by an extended right hemihepatectomy. Histologic examination revealed that the peripheral and major component of the tumor represented a fibrolamellar hepatocellular carcinoma, whereas the central, well-demarcated tumor was a less well-differentiated adult-type hepatocellular carcinoma completely encircled by the former. Cells of the peripheral tumor mass abundantly expressed cytokeratin-7, typically present in the fibrolamellar variant, whereas no cytokeratin-7 immunoreactivity was found in the central tumor. To our knowledge, this is the first reported case of a not admixed but clearly separated evolution of these 2 histologic patterns within the same tumor, and suggests that the 2 types of hepatocellular carcinoma may share a common pathogenic pathway. Topics: Adult; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Neoplasms, Multiple Primary; Treatment Outcome | 2002 |
The utility of keratin 903 as a new prognostic marker in mass-forming-type intrahepatic cholangiocarcinoma.
The cytokeratins phenotype is largely preserved during neoplastic transformation and tumor development. We evaluated the immunoreactivity of biliary epithelial markers keratin 903 and cytokeratin 7 and 19 for intrahepatic cholangiocarcinoma, and compared the results with those for biliary dysplasia and hepatocellular carcinoma. Reactivity with keratin 903 was weakly expressed and increased after the expression of cytokeratin 7 and 19 during human intrahepatic bile duct development. More than 80% of cases of biliary dysplasia showed positive reactivity with keratin 903. Of the 30 cases of hepatocellular carcinoma, 3 (10%), 6 (20%), and 1 (3%) showed positive reactivity with Keratin 903 and cytokeratin 7 and 19, respectively. Among the 73 cases of intrahepatic cholangiocarcinoma, 54 (74%), 66 (90%), and 61 (84%) showed positive reactivity with keratin 903 and cytokeratin 7 and 19, respectively. On clinicopathologic examination of intrahepatic cholangiocarcinomas, reduced keratin 903 reactivity was significantly higher in tumors with an expansive growth pattern (P <.0001), in those with medullary-type stromal reaction (P =.0327), in those without perineural invasion (P =.0001), and in those without lymph node metastasis (P =.0015). In addition, the reactivity with Keratin 903 was directly correlated with expression of cytokeratin 7 and 19 (P =.0153 and P <.0001, respectively). Cases showing reduced keratin 903 reactivity were characterized by a distinctive morphology indicating an hepatocellular carcinoma-like pattern. Multivariate analysis of overall survival revealed that keratin 903 reactivity was a significantly independent prognostic factor. In conclusion, patients with intrahepatic cholangiocarcinoma showing reduced keratin 903 reactivity had a favorable prognosis. Remarkably, the cytokeratin phenotype of intrahepatic cholangiocarcinoma was correlated with the morphologic appearance of intrahepatic cholangiocarcinoma. Topics: Aged; Autopsy; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Child, Preschool; Cholangiocarcinoma; Female; Fetus; Humans; Immunohistochemistry; Infant; Infant, Newborn; Keratins; Liver; Liver Neoplasms; Male; Middle Aged; Prognosis; Survival Analysis | 2002 |
Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma.
Distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic adenocarcinoma (MA) involving the liver can be problematic, often requiring the use of immunohistochemistry to facilitate diagnosis. Hep Par 1, a monoclonal antibody with expression confined primarily to benign and malignant hepatocytes, has recently become commercially available. We evaluated Hep Par 1 along with other immunohistochemical markers used to differentiate HCC, CC, and MA, including AE1/AE3, CAM 5.2, B72.3, monoclonal carcinoembryonic antigen (mCEA), polyclonal CEA (pCEA), alpha-fetoprotein (AFP), factor XIIIa, inhibin, CD10, villin, MOC-31, cytokeratin (CK) 7, CK 19, and CK 20, to determine the markers most useful in differentiating these entities. Forty-two cases of HCC, 9 cases of CC, and 56 cases of MA (24 colon, 15 pancreas, 8 ovary, 5 breast, and 4 stomach) were studied. Hep Par 1 was sensitive and specific for HCC, with 38 of 42 (90%) cases staining positively, whereas reactivity was observed in only 8 of 56 (14%) MAs and 0 of 9 CCs. Though limited somewhat by poor sensitivity, a bile canalicular pattern of staining with pCEA, CD10, and villin was specific for HCC and was not observed in the other tumors. Lack of mCEA and MOC-31 immunoreactivity was also characteristic of HCCs. CK 19 positivity favored CC over HCC, but was not useful in differentiating CC from MA. Expression of AFP, although observed in only about one third of the cases, favored HCC over CC and MA. CK 7 and CK 20 were also useful in this differential diagnosis, particularly when dealing with MA of colonic origin. AE1/AE3, CAM 5.2, B72.3, inhibin, and factor XIIIa were noncontributory in differentiating these entities. Topics: Adenocarcinoma; alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Carrier Proteins; Cholangiocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Microfilament Proteins; Neprilysin; Sensitivity and Specificity | 2002 |
HCC CKs are altered histones during tumor transformation in hepatoma.
The stability of cytokeratin (CK) protein during tumor transformation in human hepatocellular carcinoma (HCC) was studied with molecular approach previously. The results demonstrated that the CK was modulated in human HCC. Besides this, three low molecular weight CK molecules (named HCC CK) were found. It indicated that these HCC CKs are undergone modulation from human hepatocyte CK18. However, there were many differences between the CK18 and HCC CK. First, the antigenecity of HCC CK had been changed since they could not be recognized by CAM5.2 antibody on Western blot. Second, the sequences of N-terminal residues of HCC CK were matched with those of the N-terminal residues of human histone. In this study, we confirmed that the HCC CK was actually to be histones because they reacted to anti-histone antibody on Western blot. Furthermore, we found that the histones of human HCC had been changed during the process of tumor transformation since they could be co-immunoprecipitated with CK18 and could be detected by Western blot while this phenomenon did not happen in the normal liver tissue. We also found that not all histones change in human HCC. Only H3 was detected on Western blot while H1, H2A, H2B, and H4 were not detected in human HCCs. Topics: Blotting, Western; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Electrophoresis, Polyacrylamide Gel; Histones; Humans; Keratins; Liver Neoplasms; Precipitin Tests | 2002 |
Expression of cytokeratin 19 in human hepatocellular carcinoma cell lines.
It has been reported that the cytokeratin 19 (CK19) fragment, CYFRA 21-1, is increased in sera of some hepatocellular carcinoma patients. We hypothesized that CYFRA 21-1 might be released directly from hepatocellular carcinoma. To investigate this mechanism, we evaluated expression of CK19 in 8 human cell lines by immunoradiometric assay, Western blotting, immunohistochemistry, and reverse transcriptase-polymerase chain reaction in Chang liver cells, 2 cholangiocarcinoma cell lines, and 5 hepatocellular carcinoma cell lines. Three of 5 hepatocellular carcinoma cell lines released CYFRA 21-1, synthesized CK19 protein and expressed mRNA for CK19, as observed in 2 cholangiocarcinoma cell lines. In contrast, there was no expression of CK19 in Chang liver cells or 2 of 5 hepatocellular carcinoma cell lines. Analysis of genomic DNA for CK19 demonstrated that exon 1 was not amplified in the 3 cell lines not expressing CK19. However, there were no point mutations within exon 1 and the promoter region of CK19 in hepatocellular carcinoma cell lines. Our present study demonstrates that: i) the expression of CK19 was evident in some human hepatocellular carcinoma cell lines, and ii) the expression of mRNA for CK19 was related to the release of CYFRA 21-1. These results partially clarify the mechanism by which some hepatocellular carcinoma cell lines produce CK19 and others do not. Topics: Antigens, Neoplasm; Base Sequence; Bile Duct Neoplasms; Blotting, Western; Carcinoma, Hepatocellular; Cholangiocarcinoma; DNA Primers; DNA, Neoplasm; Gene Expression; Humans; Immunoenzyme Techniques; Immunoradiometric Assay; Keratin-19; Keratins; Liver Neoplasms; Molecular Sequence Data; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured | 2002 |
Expression of bile duct-type cytokeratin in hepatocellular carcinoma in patients with hepatitis C virus and prior hepatitis B virus infection.
The clinicopathologic findings in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) positive for biliary markers, those related to the hepatic progenitor cells, were investigated. Cytokeratin (CK) 19 was reactive for HCCs only in patients with prior hepatitis B virus (HBV) infection. The proportions of patients with prior HBV infection and poorly differentiated HCC were significantly higher among those with CK 19-positive HCC than among those with CK 19-negative HCC. Some HCCs develop from the hepatic progenitor cells in patients with HCV infection and prior HBV infection, which may affect the clinicopathologic findings of HCV-related HCCs. Topics: Aged; Bile Ducts; Carcinoma, Hepatocellular; Epithelial Cells; Female; Hepatitis B; Hepatitis B Antigens; Hepatitis B virus; Hepatitis C; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Middle Aged; RNA, Viral; Survival Rate | 2002 |
A distinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic analysis.
Chronic infections with hepatitis B (HBV) and hepatitis C (HCV) viruses are major risk factors for hepatocellular carcinoma (HCC). We have utilized a proteomic approach to determine whether a distinct repertoire of autoantibodies can be identified in HCC. Sera from 37 patients with HCC and 31 subjects chronically infected with HBV or HCV without HCC were investigated. Sera from 116 patients with other cancers, three patients with systemic lupus erythematosus, and 24 healthy subjects were utilized as controls. We report the identification of eight proteins, for each of which autoantibodies were detected in sera from more than 10% of patients with HCC but not in sera from healthy individuals (p < 0.05). Autoantibodies to four of these proteins were detected at a comparable frequency in sera from patients with chronic hepatitis. The other four proteins, which consisted of calreticulin isoforms, cytokeratin 8, nucleoside diphosphate kinase A, and F(1)-ATP synthase beta-subunit, induced autoantibodies among patients with HCC, independently of their HBV/HCV status. Calreticulin, and a novel truncated form of calreticulin (Crt32) we have identified, most commonly elicited autoantibodies among patients with HCC (27%). We conclude that a distinct repertoire of autoantibodies is associated with HCC that may have utility in early diagnosis of HCC among high risk subjects with chronic hepatitis. Topics: Adult; Aged; Antibody Specificity; Autoantibodies; Calcium-Binding Proteins; Calreticulin; Carcinoma, Hepatocellular; Case-Control Studies; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Keratins; Liver Neoplasms; Male; Middle Aged; Nucleoside-Diphosphate Kinase; Proteome; Proton-Translocating ATPases; Ribonucleoproteins | 2002 |
Elevation of cytokeratin 19 fragment in serum in patients with hepatoma: its clinical significance.
Cytokeratin 19 fragment (CK19) levels in serum have already been documented as a useful tumour marker for lung cancer. In the present study, we hypothesize that CK19 may be increased in serum from patients with hepatoma.. We measured the CK19 levels in serum from patients with hepatoma and evaluated the correlation between CK19 level and each clinical parameter. We studied 70 patients diagnosed with hepatoma, and used 14 patients with chronic hepatitis C and 45 patients with liver cirrhosis as controls.. In 33 of 70 patients (47.1%) with hepatoma, the serum CK19 level was elevated to above the normal range. CK19 levels in serum from patients with hepatoma were significantly correlated with levels of alpha-fetoprotein and prothrombin induced by vitamin K absence for factor II (PIVKA-II). In 57 patients with hepatoma in whom both CK19 and alpha-fetoprotein were measured, only CK19 was elevated in seven patients (12.3%). Immunohistochemical studies using hepatoma tissues demonstrated that hepatoma cells were stained by anti-human CK19 antibody. We also demonstrated that the HepG2 cell line expressed CK1 9.. Our data demonstrate that hepatomas aberrantly express CK19, and that measurement of CK19 might be a useful tumour marker in diagnosing hepatoma. Topics: Adult; Aged; alpha-Fetoproteins; Biomarkers, Tumor; Biopsy; Carcinoma, Hepatocellular; Female; Hepatitis C, Chronic; Humans; Immunohistochemistry; Keratins; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Tumor Cells, Cultured | 2001 |
The stability of cytokeratin 18 in human liver cells during colchicine-induced microtubule disruption.
The cytoskeleton plays important roles in cell function and is therefore implicated in the pathogenesis of many human liver diseases, including malignant tumors. The stability of cytokeratin proteins during tumor transformation in human hepatocellular carcinoma has been studied with a molecular approach previously. The results demonstrate that the cytokeratin is modulated in human hepatocellular carcinoma. Besides this, three low molecular weight cytokeratin molecules (named HCC CK) are found. This indicates that these HCC CKs have undergone modulation from the human hepatocyte cytokeratin 18. We also checked the cytokeratin profile of the human hepatoma cell line PLC/PRF/5 with the same methods to ensure the HCC CK molecules are produced by modulation but not protein degradation. The stability of cytokeratin molecules was studied by a different approach. The cytokeratin compositions of human liver cells (Chang cell line) were analysed under the effects of microtubule-disrupting drug (colchicine) by SDS-PAGE, Western blot, immunoprecipitation using a commercially available monoclonal anti-cytokeratin 18 antibody and immunofluorescent staining. Within 1 h of treatment, the microtubule began to collapse and the filamentous structure was shortening. The microtubule had almost collapsed and became fragmented to form a lattice-like network after 24 h of treatment. The cytokeratin was modulated after long-term (24 h) treatment of colchicine, and the molecular weight became 14 kD and the antigenicity was lost. The stability of cytokeratin molecules was related to the intact microtubule network, after disruption of the microtubule the cytokeratin would be modulated. The intact microtubule network was a stabilizing factor of cytokeratin 18 in human liver cells. Topics: Blotting, Western; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Colchicine; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Liver; Liver Neoplasms; Microscopy, Phase-Contrast; Microtubules; Precipitin Tests; Time Factors; Tumor Cells, Cultured | 2001 |
Primary liver carcinoma in genetic hemochromatosis reveals a broad histologic spectrum.
Hepatocellular carcinoma (HCC) is a well-known complication of genetic hemochromatosis (GH). However, the frequency of primary liver carcinoma (PLC) with biliary differentiation, such as cholangiocarcinoma (CC) and combined hepatocholangiocarcinoma (CHCC), in GH remains unclear We analyzed the histologic type of 20 PLCs occurring in the background of GH; all patients were homozygotic for the C282Y mutation. Ten were depleted of iron by successive phlebotomies, while the remaining 10 were untreated. Histologically, 13 cases were classified as HCC, 3 as CC, and 4 as CHCC. Immunohistochemical detection of Hep Par 1, cytokeratin 19 (CK19), and MUC1 supported this classification; PLC with biliary differentiation was immunoreactive for MUC1 in 86% (6/7) of cases and for CK19 in 100% (7/7) of cases. The nontumoral liver exhibited no cirrhosis or extensive fibrosis in 6 cases. Von Meyenburg complexes were present in 11 cases and intraparenchymal bile duct adenomas in 3. These data suggest that PLCs in patients with GH present a wide histologic spectrum, with tumors showing frequent biliary differentiation; may arise on a nonfibrotic or a cirrhotic liver; and often are associated with Von Meyenburg complexes and to a lesser extent with bile duct adenomas. Topics: Adenoma, Bile Duct; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Hemochromatosis; Homozygote; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Middle Aged; Mucin-1; Mutation | 2001 |
Immunohistochemical characterization of canine hyperplastic hepatic lesions and hepatocellular and biliary neoplasms with monoclonal antibody hepatocyte paraffin 1 and a monoclonal antibody to cytokeratin 7.
Immunostaining with monoclonal antibody (MoAb) hepatocyte paraffin 1 (Hep Par 1) and an MoAb to cytokeratin 7 (CK7) was performed on 105 formalin-fixed, paraffin-embedded canine hyperplastic and neoplastic hepatic lesions. Hep Par 1 was detected in 12/12 hyperplastic nodules, 17/17 hepatocellular adenomas, and 37/40 hepatocellular carcinomas. The staining was disseminated, granular, and cytoplasmic. This antibody did not react with normal or neoplastic biliary epithelium. Other hepatic tumors or tumors metastatic to the liver did not bind Hep Par 1 except one metastatic intestinal carcinoma. MoAb to CK 7 stained all hyperplastic biliary epithelium and benign cholangiocellular tumors (5/5) and 14/18 cholangiocellular carcinomas. One hepatocellular carcinoma had cells positive for both Hep Par 1 and CK 7. Liver was the only normal tissue tested that reacted with MoAb Hep Par 1. Only five nonhepatic tumors (one adrenocortical carcinoma, one interstitial cell tumor of the testis, one melanoma, and two salivary adenocarcinomas) of 277 tumors tested had focal/multifocal staining for Hep Par 1. Prolonged fixation did not alter the staining with Hep Par 1. We conclude that Hep Par 1 is a specific and sensitive marker for canine hepatocellular tumors and allows distinction between hepatocellular and biliary neoplasms. Topics: Adenoma, Liver Cell; Animals; Antibodies, Monoclonal; Bile Duct Neoplasms; Carcinoma, Hepatocellular; Dog Diseases; Dogs; Hyperplasia; Immunohistochemistry; Keratin-7; Keratins; Liver; Liver Neoplasms; Retrospective Studies | 2001 |
Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97.
To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms.. Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied.. Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10).. Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis. Topics: Albumins; alpha-Fetoproteins; Animals; Carcinoma, Hepatocellular; Cell Division; Chromosomes; Clone Cells; Flow Cytometry; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Keratins; Liver; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Tumor Cells, Cultured; Virus Integration | 2001 |
Vimentin/cytokeratin coexpression foci in a well-differentiated canine hepatocellular carcinoma.
A number of pale-stained cell foci were observed within a well-differentiated hepatocellular carcinoma which developed in a 10-year-old male mongrel dog. The foci were composed of hepatocyte-like cells, but did not contain glycogen granules in their cytoplasm. Immunohistochemically, the focus cells coexpressed both bile duct type cytokeratin and vimentin. Electronmicroscopically, they were abundant in cytoplasmic organelles and contained bile pigments. Bile canaliculi were noted between the focus cells. The focus cells in the present case were considered to be neoplastic hepatocytes expressed bipotential features of hepatic stem cells. Topics: Animals; Bile Ducts; Carcinoma, Hepatocellular; Dog Diseases; Dogs; Keratins; Male; Microscopy, Electron; Vimentin | 2000 |
Hepatocellular carcinoma metastatic to the oral mucosa: report of a case with multiple gingival localizations.
Metastases to the oral mucosa are rare, representing less than 1% of the tumors at this site. Most of these metastatic neoplasms originate in the lungs, kidneys, and liver.. The clinicopathologic features of an occult hepatocellular carcinoma, metastatic to the oral mucosa, are reported. The patient, a 70-year-old male, complained of 3 distinct polypoid, reddish lesions of the antero-inferior alveolar crest and both the right and left postero-superior attached gingiva, without bone involvement. The lesions were excised, with the clinical diagnosis of multiple vascular tumors, formalin-fixed, paraffin-embedded, cut and stained with hematoxylin and eosin. Consecutive sections were immunostained for alpha-1-antichymotrypsin, CEA, cytokeratins, EMA, hepatocyte antigen, PSA, S-100 protein, and thyroglobulin, using the alkaline phosphatase/anti-alkaline phosphatase technique.. The morphologic features of the lesions were consistent with the diagnosis of carcinoma with trabecular and glandular patterns and bile secretion; furthermore, immunohistochemical reactivity for alpha-1-antichymotrypsin, cytokeratins, CEA, EMA, and hepatocyte antigen was demonstrated and the hepatic origin of the tumor was postulated. Ultrasonography demonstrated a liver mass, which was biopsied and treated by chemoembolization. While no further complications occurred in the oral mucosa, the patient died 8 months after the diagnosis for widespread diffusion of the tumor to the lungs and brain.. This case emphasizes the need to include metastatic tumors in the differential diagnosis of atypical neoplasms of the oral mucosa and to evaluate the opportunity of surgical treatment in order to preserve the functions of the mouth, even if the prognosis of the primary tumors remains unfavorable. Topics: Aged; alpha 1-Antichymotrypsin; Biomarkers, Tumor; Brain Neoplasms; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Diagnosis, Differential; Fatal Outcome; Gingival Neoplasms; Humans; Keratins; Liver Neoplasms; Lung Neoplasms; Male; Mucin-1; Polyps; Vascular Neoplasms | 2000 |
Hepatoid adenocarcinoma of the rectum arising in ulcerative colitis: report of a case.
We report a case of intestinal hepatoid adenocarcinoma, confirmed by albumin m-RNA in situ hybridization, with subsequent metastatic spread to the liver in a male with a long-standing history of ulcerative colitis. This novel finding strongly suggests that ulcerative colitis can lead not only to conventional adenocarcinomas but also to hepatoid adenocarcinoma and highlights the mimicry of hepatocellular carcinoma by metastatic hepatoid adenocarcinoma liver nodules. Topics: Adenocarcinoma; Adult; Albumins; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Colitis, Ulcerative; Colonic Polyps; Follow-Up Studies; Humans; In Situ Hybridization; Keratins; Liver Neoplasms; Lymphatic Metastasis; Male; Mucin-1; Rectal Neoplasms; RNA, Messenger | 2000 |
Atypical presentation of hepatocellular carcinoma.
Hepatocellular carcinoma is relatively rare in the United States, and the patterns of extrahepatic manifestations are diverse. Disease dissemination occurs through hematogenous routes to frequently involve the lungs, bone, adrenal glands, and pancreas. Soft tissue metastasis is extremely rare and mandates systematic pathologic analysis, which may include the use of immunohistochemical staining for tumor-specific markers. Relevant tumor markers that can assist in localizing the site of origin for adenocarcinoma include carcinoembryonic antigen, alpha-fetoprotein, vimentin, and anticytokeratins. We detail the utility of immunohistochemistry in evaluating tumors of unknown origin. Topics: Aged; alpha-Fetoproteins; Biomarkers, Tumor; Biopsy; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Soft Tissue Neoplasms; Vimentin | 2000 |
Role of phosphorylation in ethanol-induced aggregation of keratin intermediate filaments.
Keratins are members of a diverse group of tissue-specific cytoskeletal components known as intermediate filaments. Regulation of the structure and intracellular distribution of intermediate filaments is known to be related to the phosphorylation state of their structural subunits. It also is known that disruption of the keratin filaments of hepatocytes in response to chronic ethanol ingestion is characteristic of alcoholic liver disease.. To characterize the mechanism of ethanol-induced keratin filament reorganization and dephosphorylation, cells were grown in culture with and without ethanol, and then were treated at the end of the incubation period for 1 hr with either 8-bromo-adenosine 3':5'-cyclic monophosphate (8Br), water-soluble forskolin (ws-forskolin), H-89 diHCL, or okadaic acid. Morphology of the cells was examined by immunofluorescence microscopy, and keratin phosphorylation levels were determined by analysis of 32p labeling.. We found that treatment of hepatoma cells with 300 mM ethanol results in disruption and aggregation of the keratin network in the vicinity of the nucleus as well as a hypophosphorylation of keratin subunits from ethanol-treated cells compared with non-ethanol-treated controls. 8Br and ws-forskolin treatment of ethanol groups restored keratin phosphorylation to control levels and reversed the ethanol-induced aggregation of keratin filaments. When H-89, an inhibitor of A-kinase, was added to control cells, keratin filament disorganization and dephosphorylation was observed. H-89 produced only a slight additional decrease in keratin phosphorylation in ethanol-treated cells, with no change in keratin distribution. Okadaic acid treatment of control cells produced hyperphosphorylation and filament network disruption, whereas in ethanol groups a reversal of the ethanol-mediated hypophosphorylation was observed but without reversal of the keratin filament aggregation.. These results suggest that site-specific phosphorylation of keratin filaments is important in maintaining their integrity and that activation of the A-kinase system can antagonize the effects of ethanol, whereas its inhibition results in filament dephosphorylation and reorganization, mimicking effects of ethanol treatment. Topics: Animals; Carcinoma, Hepatocellular; Central Nervous System Depressants; Cyclic AMP-Dependent Protein Kinases; Enzyme Inhibitors; Ethanol; Hepatocytes; Intermediate Filaments; Isoquinolines; Keratins; Phosphorylation; Rats; Sulfonamides; Tumor Cells, Cultured | 2000 |
Do the CK18 related proteins change in general in epithelial cancers?
The modulation of cytokeratin 18 during tumor transformation in hepatoma had been previously recognized through a series of biochemical and immunological approaches. Expression of cytokeratin 18 in transitional cell carcinoma comparing with hepatoma was investigated using the hepatoma transformation model. CK18 related molecules were found. In the present study, we design various epithelial cancers with the same model. CK18 related molecules were all evident. Therefore, we suggest that CK18 related proteins would play an important role in tumorigenesis of epithelial cancers. Topics: Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Female; Humans; Keratins; Liver Neoplasms; Male; Molecular Weight; Neoplasm Proteins; Neoplasms, Glandular and Epithelial | 2000 |
Angiomyolipoma of the liver in fine-needle aspiration biopsies: its distinction from hepatocellular carcinoma.
Angiomyolipoma (AML) of the liver is an uncommon benign lesion that may be difficult to distinguish clinically, radiographically, and morphologically from hepatocellular carcinoma (HCC).. Fine-needle aspiration biopsies (FNAB) of three AMLs of the liver were compared with FNABs from eight cases of HCC. Immunoperoxidase stains for HMB-45, muscle specific actin, and CAM 5.2 were performed on two cell blocks and one resection of AML.. All three AMLs yielded cellular aspirates. They were composed of clusters of cells with arborizing transgressing endothelium but no peripherally wrapping endothelium. Smooth muscle cells of AML showed fibrillar cytoplasm and indistinct cytoplasmic borders; HCC showed granular cytoplasm and distinct cytoplasmic borders. Extramedullary hematopoiesis was present only in AML. Mitotic figures were seen only in HCC. Intranuclear inclusions, nucleoli, and large, atypical cells were present in both AML and HCC. Fat was seen in only one case of AML and was scant. Immunoperoxidase stains for HMB-45 and smooth muscle actin were positive in AML and negative in adjacent normal liver. CAM 5.2 stain was negative in AML.. The cytologic features seen on FNABs of AML are distinct from those of HCC. Immunoperoxidase stains can aid in the definitive diagnosis on FNAB. It is important to recognize AML on FNAB to allow conservative clinical management. Topics: Actins; Adult; Aged; Aged, 80 and over; Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Hepatocellular; Diagnosis, Differential; Female; Hematopoiesis, Extramedullary; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Melanoma-Specific Antigens; Middle Aged; Muscle, Smooth, Vascular; Neoplasm Proteins | 1999 |
An immunohistochemical study of hepatic atypical adenomatous hyperplasia, hepatocellular carcinoma, and cholangiocarcinoma with alpha-fetoprotein, carcinoembryonic antigen, CA19-9, epithelial membrane antigen, and cytokeratins 18 and 19.
Eight hepatic atypical adenomatous hyperplasias (AH), 30 hepatocellular carcinomas (HCC) consisting of 11 well-, 13 moderately and six poorly differentiated HCC, and 10 intrahepatic cholangiocarcinomas (CC) were investigated immunohistochemically with anti-alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA19-9, epithelial membrane antigen (EMA), and cytokeratins (CK) 18 and 19 antibodies. Immunostaining was regarded as positive when more than 5% of cells were stained. Alpha-fetoprotein was positive, although focally, in five (17%) of 30 HCC but negative in all AH and CC. Carcinoembryonic antigen (polyclonal antibody) did not stain the cytoplasm of all AH and HCC, but stained two (25%) of eight AH and 10 (33%) of 30 HCC in a bile canalicular staining manner. Carcinoembryonic antigen showed intracytoplasmic or luminal border staining in six (60%) of 10 CC. CA19-9 was negative in all AH and HCC, while six (60%) of 10 CC were positive for CA19-9. Epithelial membrane antigen was positive in one (13%) of eight AH, seven (23%) of 30 HCC and in all 10 cases of CC. Cytokeratin 18 was positive in all AH, HCC and CC. Cytokeratin 19 was negative in both AH and HCC, whereas it stained the cytoplasm of tumor cells in all CC diffusely and intensely. These results suggest that immunostaining of AFP, CEA, CA19-9, EMA, CK18 and CK19 are not useful in the differential diagnosis between AH and well-differentiated HCC, and that CK19 is the most suitable reagent for the differential diagnosis between HCC and CC. Topics: Adenoma; alpha-Fetoproteins; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Humans; Hyperplasia; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Mucin-1; Precancerous Conditions; Predictive Value of Tests; Prognosis | 1999 |
Expression of MUC1, Thomsen-Friedenreich antigen, Tn, sialosyl-Tn, and alpha2,6-linked sialic acid in hepatocellular carcinomas and preneoplastic hepatocellular lesions.
The expression of epithelial mucins and Thomsen-Friedenreich-related antigens in preneoplastic and neoplastic hepatocellular lesions was systematically investigated using an in situ immunohistochemical staining approach. MUC1, MUC2, TF, sialosyl-TF, Tn, sialosyl-Tn, alpha2,3-linked sialic acid, and alpha2,6-linked sialic acid were examined in normal and cirrhotic human liver and in human hepatocellular carcinomas (HCCs) and cholangiocarcinomas. Normal hepatocytes and preneoplastic foci of altered hepatocytes did not express MUC1, MUC2, TF, Tn, s-Tn, or alpha2,6-linked sialic acid. In contrast, HCCs showed positive reactions for MUC1, TF, Tn, s-Tn, and alpha2,6-linked sialic acid. MUC2 was absent in normal biliary epithelial cells, but present in cholangiocarcinomas. The staining of MUC1, or s-Tn and alpha2,6-linked sialic acid in human normal liver tissues and various liver diseases did not change after specific treatments such as periodate oxidation or saponification, indicating that their expression in HCC does not result from incomplete glycosylation or low O-acetylation, respectively. MUC1, TF, Tn, s-Tn, and alpha2,6-linked sialic acid may be useful as indicators of progression of HCC in tissue sections, and perhaps also as targets for diagnostic and therapeutic approaches in vivo. Topics: Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Hepatocellular; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Mucin-1; N-Acetylneuraminic Acid; Precancerous Conditions | 1999 |
Expression of biliary antigen and its clinical significance in hepatocellular carcinoma.
In order to classify the hepatocellular carcinomas (HCCs) which had diverse clinicopathologic characteristics, we divided HCCs into two groups according to the expression of biliary antigen on the basis of the hypothesis that the hepatocyte and biliary epithelial cell originate from the same precursor cell, and then we investigated the clinical and pathologic characteristics in the two groups. Forty HCC cases with no preoperative treatment and at least two-year follow-up data were selected among 202 cases of HCC files from 1991 to 1995. Expression of biliary antigen (AE1, cytokeratin 19), p53, AFP, and Ki-67 in the tumor tissue were assessed by immunohistochemistry. Positive cytokeratin 19 was noted in one case (2.5%); AE1 was detected in 40% of patients; p53 was overexpressed in 20% of patients; and AFP was detected in 45% of patients. No statistical difference between the biliary antigen positive group (16 cases) and the negative group (24 cases) were noted in terms of mean age, sex, presurgical serum AFP level, Child class, and tumor size. HBsAg positive rate was 66.7% for the biliary antigen (-) group and 93.8% for the biliary antigen (+) group with a statistically significant difference (p = 0.048). The number of cases for Edmonson-Steiner grade I/II and III/IV were 15 and 9 in the biliary antigen (-) group, and 4 and 12 in the biliary antigen (+) group, respectively, with a statistically significant difference (p = 0.024). The 1, 3 and 5-year disease-free survival rates were 69.7, 40.9 and 40.9% for the biliary antigen (-) group and 73.7, 39.1, 39.1% for the biliary antigen (+) group with no statistically significant difference. The 1, 3 and 5-year overall survival rates were 91.7, 73.8, 66.4% for the biliary antigen (-) group and 68.8, 34.4, 34.4% for the biliary antigen (+) group, with a significantly greater overall survival rate for the biliary antigen negative group (p = 0.045). Poor histopathological differentiation, a high HBsAg positive rate and poor overall survival rate were noted in the biliary antigen positive group and the differences were statistically significant. In conclusion, HCCs with positive biliary antigen, which originates from more primitive cells, is suggested to be more aggressive than HCCs with negative biliary antigen. Topics: Adult; Aged; alpha-Fetoproteins; Bile Ducts; Carcinoma, Hepatocellular; Female; Humans; Keratins; Ki-67 Antigen; Liver Neoplasms; Male; Middle Aged; Prognosis; Survival Rate; Tumor Suppressor Protein p53 | 1999 |
Hepatocellular carcinoma expressing both hepatocellular and biliary markers also expresses cytokeratin 14, a marker of bipotential progenitor cells.
Topics: Biomarkers; Carcinoma, Hepatocellular; Female; Gallbladder; Humans; Keratin-14; Keratins; Liver Neoplasms; Male; Middle Aged; Stem Cells | 1999 |
High levels of BCL-2 messenger RNA detected by in situ hybridization in human hepatocellular and cholangiocellular carcinomas.
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. Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; In Situ Hybridization; Keratins; Liver Neoplasms; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger | 1999 |
The expression of cytokeratin 18 in transitional cell carcinoma comparing with hepatoma.
The epithelium in kidneys and urinary bladders contain CK18 as in liver cells. The modulation of cytokeratin 18 during tumor transformation in hepatoma had been previously recognized through a series of biochemical and immunological approaches. A 14 KD hepatoma related molecules was found in the previous studies. We would like to utilize the hepatoma transformation model to study the changes in CK18 in transitional cell carcinoma, using immunoblotting and western blotting techniques. The result is that transitional cell carcinoma retain their CK18 molecule. Furthermore, CK18 related molecules similar to those seen in hepatoma also present in transitional cell carcinoma. The conclusions are transitional cell carcinoma contains CK18 related proteins similar to those seen in hepatoma tissues. We suggest that this element would be responsible for the change during the malignant transformation processes. Topics: Blotting, Western; Carcinoma, Hepatocellular; Carcinoma, Transitional Cell; Keratins; Kidney Neoplasms; Liver Neoplasms; RNA, Messenger; Urinary Bladder Neoplasms | 1999 |
De novo expression of nonhepatocellular cytokeratins in Mallory body formation.
Mallory bodies (MBs) are eosinophilic cytoplasmic inclusions observed predominantly in alcoholic liver disease. Although linked to disease activity, their pathogenesis is still unclear. Since intermediate filaments (cytokeratins) are major components of MBs, their cytokeratin polypeptide composition was analysed with monospecific antibodies for cytokeratins 7, 8, 14, 18, 19, and 20 by immunohistology. MBs were identified by light microscopy and ubiquitin immunostaining. All MBs were positive for cytokeratins 8 and 18. A significant percentage of the MBs was strongly positive for cytokeratins 19 and/or 20, which are not detectable in hepatocytes of normal liver and, in the case of cytokeratin 20, in hepatocytes of diseases devoid of MBs. MBs were essentially negative for cytokeratins 7 and 14. De novo expression of cytokeratins 19 and 20 was independent of the aetiology, occurring in all MB-associated diseases analysed, and seemed to precede MB formation, since in some hepatocytes a cytoskeletal-type staining pattern for these cytokeratins was present. In hepatocellular carcinomas cytokeratins 19 and 20 were frequently detected, but their cellular distribution was less closely associated with MBs. The ectopic expression of cytokeratins 19 and 20 appears to be related to MB formation and may take part in the derangement of the intermediate filaments during MB formation. Topics: Antibodies, Monoclonal; Carcinoma, Hepatocellular; Child; Hepatolenticular Degeneration; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Liver; Liver Cirrhosis; Liver Diseases; Liver Diseases, Alcoholic; Liver Neoplasms | 1998 |
Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomas.
Transactivation of cellular genes and functional inactivation of p53 by the hepatitis B virus (HBV) X gene-encoded protein (HBx) are proposed as alternative mechanisms for induction of hepatocellular carcinomas (HCCs) in chronic HBV infection. Using an immunohistochemical approach, we studied the expression of HBx in 39 explanted livers with HBV-associated disease. Because the data reported previously have been inconsistent, possibly due to the application of different antibodies, we compared results with 5 polyclonal and 6 monoclonal anti-HBx antibodies from five laboratories. Ten of the 11 antibodies reacted with recombinant HBx by Western blotting, but only 1 polyclonal and 2 monoclonal antibodies reacted specifically with HBx in tissue, and were thus suitable for immunohistochemistry. Three other polyclonal antibodies reacted with tissue components in addition to HBx. One polyclonal and 4 monoclonal antibodies did not recognize the HBx in the tissue. HBx was demonstrated in 16 of 30 (53.3%) cirrhotic livers and 10 of 18 (58.8%) HCCs by all specific antibodies. The expression of HBx, among three HBV antigens examined, was found to be preferentially maintained in HCC and the surrounding liver parenchyma, including focal or nodular preneoplastic lesions. However, the immunoreactivity was always limited to the cytoplasm of a small number of parenchymal and neoplastic cells. The role of X gene expression in HBV-associated human hepatocarcinogenesis remains to be established. Topics: Animals; Carcinoma, Hepatocellular; Hepatitis B; Humans; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Rabbits; Trans-Activators; Viral Regulatory and Accessory Proteins | 1998 |
Prevention of ornithine cytotoxicity by proline in human retinal pigment epithelial cells.
To investigate the relationship between ornithine-delta-aminotransferase (OAT) deficiency and ornithine accumulation and the specific degeneration of retinal pigment epithelial (RPE) cells in gyrate atrophy.. Human RPE cells, human hepatoma cells, and human fibroblast cells were treated with 5-fluoromethylornithine (5-FMOrn), a specific irreversible inhibitor of OAT. Ornithine cytotoxicity was determined by using a [3H]thymidine incorporation assay and immunohistochemical staining for cytokeratin. The effects of various metabolites of ornithine and arginine, such as creatine, creatine phosphate, I-delta 1-pyrroline-5-carboxylic acid (L-P5C), and proline, which may be deficient in gyrate atrophy on RPE cell damage by ornithine, were determined by the same procedures.. When the human RPE cells, HepG2 hepatoma cells, and WI-38 fibroblast cells were treated with 0.5 mM 5-FMOrn for 30 minutes, which inactivated OAT, ornithine exhibited severe time- and dose-dependent inhibition of DNA synthesis in the human RPE cells but not in the HepG2 hepatoma cells or WI-38 fibroblast cells. The inhibition of DNA synthesis was accompanied by drastic changes in morphologic appearance, disorganization of the cytoskeleton, and cell death. Ornithine or 5-FMOrn alone did not exhibit such cytotoxicity to the RPE cells. Proline prevented the cytotoxicity of ornithine.. These findings suggest that an elevated level of ornithine combined with an increased sensitivity to ornithine as a result of OAT deficiency may be crucial to the specific RPE degeneration in gyrate atrophy. They suggest also that abnormalities of proline metabolism may be involved in the progress of gyrate atrophy. Topics: Arginine; Carcinoma, Hepatocellular; Cell Death; Cell Division; Cell Line; Cell Survival; DNA; DNA Replication; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fibroblasts; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Liver Neoplasms; Ornithine; Ornithine-Oxo-Acid Transaminase; Pigment Epithelium of Eye; Proline | 1998 |
Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.
CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC. Topics: alpha-Fetoproteins; Antigens, Neoplasm; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Female; Humans; Keratin-19; Keratins; Liver Neoplasms; Male; Middle Aged; Protein Precursors; Prothrombin; Tomography, X-Ray Computed | 1998 |
Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma.
To examine the usefulness of Hep Par 1 together with selected antibodies in the separation of hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC), combined tumours (HCC-CC) and metastatic carcinoma.. Antibodies to Hep Par 1, CK19, CK20 and factor XIIIa were applied to 32 HCCs, 27 CCs, five HCC-CCs and 19 metastatic carcinomas from a variety of sites. Hep Par 1 produced distinctive granular staining of all benign hepatocytes and stained 30 HCCs in a heterogeneous manner, irrespective of the degree of differentiation. While labelling all cases of combined HCC-CC, the antibody also stained the mucus-secreting cells of four cases of pure CC. Anti-CK19 produced distinctive staining of bile ducts and CC but also decorated four HCCs and 10 metastatic tumours. Factor XIIIa was not found in normal, reactive or neoplastic hepatocytes. CK20 was found in some cases of HCC and CC and in all cases of metastatic carcinomas from the colon.. Hep Par 1 was a sensitive marker of hepatocytes but its variable staining in HCC may produce false negative results in small biopsies and it was occasionally found in CC. The highest diagnostic yield was obtained when anti-Hep Par 1, CK19 and CK20 were used in a panel. Factor XIIIa staining has no role in the diagnosis of liver cancers. Topics: Antibodies; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Differentiation; Cholangiocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Liver Neoplasms; Neoplasms, Multiple Primary; Transglutaminases | 1998 |
[Clear cell hepatocellular carcinoma: significance of CK 19].
Topics: Carcinoma, Hepatocellular; Humans; Keratins; Liver Neoplasms; Male; Middle Aged | 1998 |
The alteration of cytokeratin 18 molecule and its mRNA expression during tumor transformation in hepatoma.
The cytokeratin 18 related molecules of human hepatocellular carcinoma have been previously recognized through a series of biochemical and immunological approaches. It is suggested that these molecules undergo modulation from human hepatocyte cytokeratin 18. To prove whether these molecules are produced by modulation or protein degradation, we checked the cytokeratin profile of human hepatoma cell line PLC/PRF/5 with the methods used before. These results revealed that the PLC cells have the same cytokeratin 18 related molecules as human hepatocellular carcinoma tissue. The gene expression of the cytokeratin 18 in non-tumor liver tissues, hepatocellular carcinoma and PLC/PRF/5 cells were investigated. First, the mRNAs of non-tumor liver tissues, hepatocellular carcinoma tissues and PLC/PRF/5 cells were collected by the acid guanidinium thiocyanate phenol chloroform method. After transcription into cDNA by reverse transcriptase polymerase chain reaction, the cDNAs of each specimen were amplified by PCR and then digested by SmaI and BamHI restriction enzymes. The digested cDNA fragments were electrophoresed in agarose gel and the base pairs were found to be the same in length between neoplastic and non-neoplastic hepatocytes. Topics: Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Humans; Keratins; Liver Neoplasms; Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured | 1997 |
Hepatoid adenocarcinoma of the lung: report of a case of an unusual alpha-fetoprotein-producing lung tumor.
We report on a rare tumor of the lung characterized by its morphologic hepatoid features and alpha-fetoprotein production. This unusual neoplasm arose in the left lung of a 36-year-old man in whom clinical and radiologic examinations did not reveal any other tumor. The serum level of alpha-fetoprotein was measured at 6,090 ng/mL and was parallel to the evolution of the tumor. Despite treatment, the patient died 7 months after the diagnosis. The microscopic appearance of the tumor was the same as observed in hepatocarcinoma and hepatoid adenocarcinoma of the ovary or the stomach, with a tubular, papillary, or trabecular pattern. Periodic acid-Schiff-positive hyaline globules were numerous, and tumor cells showed immunohistologic positivity for alpha-fetoprotein and carcinoembryonic antigen. This lung adenocarcinoma was first described by Ishikura et al. in 1990 and was named hepatoid lung adenocarcinoma. Like the rare hepatoid carcinoma of the gallbladder, the pancreas, the ampulla of Vater, the renal pelvis, and the bladder, the exact histogenesis and the prognosis of this type of lung tumor are not yet known. Topics: Adenocarcinoma; Adult; alpha-Fetoproteins; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung; Lung Neoplasms; Magnetic Resonance Imaging; Male; Mucin-1; Prognosis; Time Factors | 1997 |
Cytokeratin 18 is expressed on the hepatocyte plasma membrane surface and interacts with thrombin-antithrombin complexes.
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. Topics: Animals; Antibodies; Antithrombin III; Binding, Competitive; Carcinoma, Hepatocellular; Cattle; Cell Membrane; Gene Products, tat; Humans; Keratins; Liver; Liver Neoplasms; Peptide Hydrolases; Perfusion; Rabbits; Rats; Surface Properties; Tumor Cells, Cultured | 1997 |
[Sarcomatous hepatocellular carcinoma].
Atypical variants of liver carcinomas may represent diagnostic pitfalls when compared with classical types. We described two cases of unusual hepatocellular carcinoma with sarcomatoid pattern. Both were large tumors in elderly people. Their immunohistochemical investigation showed a coexpression of various epithelial and mesenchymal markers. There were positivities of antibodies against cytokeratin, actin and desmin in the first case, against cytokeratin, chromogranin and actin in the second case and against EMA and A1AT in both of them. Such a tumor was not found either in five year bioptic and four year necroptic archival material or in the Hlava Institute histopathological collection. The frequency of the tumor was about 4% of all hepatocellular carcinomas according to the literature. Topics: Actins; Aged; Carcinoma, Hepatocellular; Desmin; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Sarcoma | 1997 |
Histogenesis of primary liver carcinomas: strengths and weaknesses of cytokeratin profile and albumin mRNA detection.
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. Topics: Aged; Carcinoma, Hepatocellular; Cholangiocarcinoma; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Liver Neoplasms; Male; Middle Aged; RNA, Messenger; Serum Albumin | 1996 |
Liver tumors and possible preneoplastic lesions, induced by a food-derived heterocyclic amine in cynomolgus monkeys; a study of histology and cytokeratin expression.
A food-derived mutagenic heterocyclic aromatic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), is a potent hepatocarcinogen in cynomolgus monkeys. In an ongoing carcinogenesis study, 34 out of 40 monkeys dosed with IQ have developed malignant liver tumors. The histology and cytokeratin expression was examined in a total of 94 tumors and non-neoplastic lesions obtained from 34 cases. The majority of the tumors were classified as hepatocellular carcinoma. In some cases, a striking difference in the histological features between individual tumor nodules was suggestive of a multicentric origin. Intrahepatic vascular invasion was seen in 14 (41.2%) and metastases in 6 (17.6%) of the hepatocellular carcinoma cases. There was no evidence of regenerative hyperplasia or fibrosis in the parenchyma of the tumor-bearing livers. Clear-cell foci composed of glycogen-rich hepatocytes were the only macroscopic lesions detected prior to gross tumor development. Other liver lesions included dysplastic hepatocyte foci and areas of proliferating bile ductular like (oval) cells, located around the periportal areas and along the portal tracts. Expression of bile duct type cytokeratin 7 was observed in a few of the oval cells and non-malignant hepatocytes, as well as in some of the hepatocellular carcinoma nodules. This aberrant cytokeratin expression raises questions concerning the histogenesis of the IQ-induced hepatocellular carcinoma. Topics: Animals; Bile Ducts, Intrahepatic; Carcinogens; Carcinoma, Hepatocellular; Food; Immunohistochemistry; Keratins; Liver Neoplasms, Experimental; Macaca fascicularis; Macaca mulatta; Mutagens; Neoplasm Metastasis; Neovascularization, Pathologic; Precancerous Conditions; Quinolines | 1996 |
Cytokeratin profiles and mucin secretion in combined hepatocellular-cholangiocarcinoma. A case report.
A case of a combined hepatocellular-cholangiocarcinoma (HCC-CC) is presented showing mucin production in both the HCC and the CC component. Immunohistochemical staining for cytokeratins 7 and 19 was performed and it is concluded that immunoreactivity for cytokeratin 7 and 19 is an additional criterion to the detection of mucin in making the diagnosis of a combined HCC-CC of the transitional type. Topics: Carcinoma, Hepatocellular; Cell Differentiation; Cholangiocarcinoma; Female; Humans; Keratins; Liver Neoplasms; Middle Aged; Mucins; Neoplasms, Multiple Primary | 1996 |
Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications.
Hepatocellular carcinoma (HCC) is a heterogeneous disease. HCC derived from different stages of cellular differentiation may have different clinical and pathobiological behavior. To test the hypothesis that HCC can be classified into two types based on its phenotypic markers (hepatocellular and biliary differentiation), liver tissues from 290 Chinese patients with HCC were studied. Expression of hepatocytic differentiation marker (HEP-PAR-reactive antigen), biliary differentiation markers (AE1-AE3, cytokeratin-19), proliferation markers (Ki-67, proliferating cell nuclear antigen), alpha-fetoprotein, p53, and transforming growth factor-alpha in the tumor tissue were assessed by immunohistochemistry. Hepatocytic differentiation marker was detected in 99.7% and biliary differentiation markers were detected in 29.3% of these tumors. Clinically, no patient with HCC with biliary markers survived for more than 27 weeks compared with a 22.6% survival rate in patients with HCC negative for biliary markers. HCCs positive for the biliary differentiation markers showed features of more aggressive disease in terms of poorer cellular differentiation (P < 0.001) and high-level expression of proliferation markers (Ki-67, P < 0.001; proliferating cell nuclear antigen, P = 0.0114) compared with HCCs without biliary markers. HCCs with biliary markers also had a higher level of expression of alpha-fetoprotein (P < 0.001) and p53 (P = 0.0077). Classification of HCCs based on its phenotypic (differentiation) markers has both clinical and pathobiological implications. Topics: Adult; Aged; Aged, 80 and over; Antigens, Differentiation; Bile Ducts; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Division; Female; Humans; Keratins; Ki-67 Antigen; Liver; Liver Neoplasms; Male; Middle Aged; Proliferating Cell Nuclear Antigen; Survival Rate | 1996 |
A clinicopathological study on combined hepatocellular and cholangiocarcinoma.
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. Topics: Aged; Carcinoma, Hepatocellular; Cholangiocarcinoma; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasms, Multiple Primary | 1996 |
The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver.
We performed immunohistochemical studies on 90 surgically resected liver tumors, including 30 tumors each from hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and metastatic colorectal adenocarcinoma (MCA), using monoclonal antibodies against cytokeratin (CK) 7, CK 19, and CK 20 to examine the differences in the CK expressions in primary and metastatic carcinomas of the liver. We also investigated the usefulness of such expression in the differential diagnosis in addition to existing markers such as alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9. For CK 7, all except for one (97%) of the CCs were diffusely positive, whereas only two (7%) HCCs and one (3%) MCAs were diffusely positive. For CK 19, 23 (77%) CCs and 19 (64%) MCAs were diffusely positive, whereas no HCCs were positive. For CK 20, 22 (74%) MCAs were diffusely positive, whereas no HCC and three (10%) CCs were diffusely positive. The findings concerning the expression of immunohistochemical CK are therefore considered to be useful in addition to the diagnostic criteria when making a differential diagnosis of primary and metastatic carcinomas of the liver. Topics: Adenocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Colorectal Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratins; Liver Neoplasms | 1996 |
Mutational analysis of the p53 and K-ras genes and allelotype study of the Rb-1 gene for investigating the pathogenesis of combined hapatocellular-cholangiocellular carcinomas.
Because combined hepatocellular-cholangiocellular carcinoma is rare and its biological features and pathogenesis have not been well established, we investigated alterations of the p53, K-ras and Rb-1 genes, as well as expression patterns of carcinoembryonic antigen and keratin, in seven combined hepatocellular-cholangiocarcinomas out of 557 hepatocellular carcinomas autopsied at Tokyo University during 30 years. Mutations of the p53 gene were found in two cases, at codon 244 (GGC to TGC) in the cholangiocellular carcinoma component of case 1 (mixed type, showing an intimate intermingling of both elements) and at codon 234 (TAC to AAC) in both components of case 5 (combined type, consisting of contiguous but independent masses of both elements). Mutation of the K-ras gene (codon 12, GGT to GAT) was seen only in the cholangiocellular carcinoma component of clinically apparent double cancer, case 6. Allelic alteration of the Rb-1 gene was observed in two cases, deletion of both alleles in the hepatocellular carcinoma component of case 3 (combined type) and replication error of the same pattern in both components of case 4 (mixed type). Immunohistochemical analysis showed that the hepatocellular carcinoma components of five cases (cases 2, 3, 5, 6, 7) were immunoreactive for keratin, suggesting biliary epithelial transformation. In four of the five cases (cases 3 and 5 combined, case 7 mixed and case 6 double cancer), cholangiocellular carcinoma components were also positive for keratin. These results suggest that both components of combined hepatocellular-cholangiocarcinoma have the same genetic and phenotypic character and might have arisen from the same origin in some cases. Topics: Aged; Alleles; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholangiocarcinoma; DNA Mutational Analysis; Female; Gene Deletion; Genes, p53; Genes, ras; Genes, Retinoblastoma; Humans; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Proteins; Neoplasms, Multiple Primary | 1996 |
A comparison of methods for heat-mediated antigen retrieval for immunoelectron microscopy: demonstration of cytokeratin No. 18 in normal and neoplastic hepatocytes.
Postembedding antigen retrieval is a well established technique for immunoelectron microscopy; however, many antigens cannot be detected without additional unmasking procedures. This study was undertaken to determine whether microwave oven heating, autoclaving, and pressurized boiling, which are well recognized methods of antigen retrieval for light microscopy, and simple boiling can also be used in electron microscopy. We investigated neoplastic and normal hepatocytes using a commercially available mouse monoclonal antibody against cytokeratin NO. 18 (CK 18). The tissue was fixed in paraformaldehyde/glutaraldehyde and embedded in Lowicryl K4M at -40 C. Ultrathin sections in various buffers were exposed to heat using one of four methods or to pronase at 37 C before incubation with the primary antibody. The secondary antibody was gold-labeled goat anti-mouse antibody. Sections that were not heat-treated remained unlabeled, but heat-treated sections showed immunoreactivity located mainly at the cytoplasmic periphery. Some of the gold particles lay in direct or loose association with intermediate filaments, some were seen in the area of desmosomes, and some did not appear related to any structures. No difference in immunostaining was found among the four methods of heat treatment. The citrate buffer, pH 6.0, and 10 mM EDTA, pH 8.0, generated the best labeling results. Topics: Antigens; Carcinoma, Hepatocellular; Heating; Humans; Immunoenzyme Techniques; Keratins; Liver; Liver Neoplasms; Microscopy, Immunoelectron | 1996 |
Insulin-like growth factor II regulation of gene expression in rat and human hepatomas.
Insulin-like growth factor II (IGF II) regulated tissue-specific gene expression in hepatoma cell lines, but had no effect on expression of tissue-specific genes in primary cultures of E14 and newborn rat liver cells depleted of erythroid cells. No change was observed in these primary cultures with respect to alpha-fetoprotein (alpha-FP), albumin, cytokeratin 19 (CK19), gamma-glutamyltranspeptidase (GGT), and IGF II receptors. Two well-differentiated hepatoma, HepG2 and FTO-2B, and a poorly differentiated hepatoma, H4AzC2, did not show increased proliferation in the presence of IGF II, yet showed gene expression changes in response to IGF II. In HepG2 cells, IGF II increased albumin mRNA levels and resulted in a shift from clusters of cells positive to 100% of the cells expressing immunohistochemically detectable albumin. The transcription factor HNF-3 beta mRNA and protein levels of the bile duct markers, CK19 and GGT, were also increased in the presence of IGF II. Other genes tested were not affected, including alpha-1-antitrypsin, and two liver-specific transcription factors, HNF-4 and HNF-3 alpha. In FTO-2B cells, IGF II increased the expression of albumin, CK19, and GGT, without accompanying changes in albumin and GGT mRNAs. In H4A7C2 cells, IGF II reduced CK19 and OC.3 protein levels and GGT, transferrin, and HNF-3 beta mRNAs. The effects of IGF II on H4AZC2 cells were not blocked in the presence of an anti-rat IGF II receptor antibody. We conclude that IGF II affects tissue-specific gene expression of hepatomas and qualitative and quantitative aspects of its influence on the hepatomas is dependent on their degree of differentiation. Topics: Albumins; alpha-Fetoproteins; Animals; Carcinoma, Hepatocellular; Cell Division; gamma-Glutamyltransferase; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Insulin-Like Growth Factor II; Keratins; Liver Neoplasms; Liver Neoplasms, Experimental; Rats; Rats, Inbred F344; Receptor, IGF Type 2; RNA, Messenger; Transferrin; Tumor Cells, Cultured | 1995 |
Expression of an epidermal keratin protein in liver of transgenic mice causes structural and functional abnormalities.
To examine the role of keratin intermediate filament proteins in cell structure and function, transgenic mice were isolated that express a modified form of the human K14 keratin protein in liver hepatocytes. A modified K14 cDNA (K14.P) sequence was linked downstream of the mouse transthyretin (TTR) gene promoter and enhancer elements to achieve targeted expression in hepatocytes. Hepatocytes expressing high levels of the transgene were found to have abnormal keratin filament networks as detected by indirect immunofluorescence using an antibody specific for the transgene product. Light and electron microscopic level histological analysis of isolated liver tissue showed in many cases degenerative changes that included inflammatory infiltration, ballooning degeneration, an increase in fat containing vacuoles, and glycogen accumulation. These changes were most evident in older mice over four months of age. No indication of typical Mallory body structures were identified at either the light or electron microscopic level. To evaluate secretory function in transgenic livers, bile acid secretion rates were measured in isolated perfused liver and found to be approximately twofold lower than aged-matched controls. These findings indicate that expression of an abnormal keratin in liver epithelial cells in the in vivo setting can alter the structure and function of a tissue and suggest a role of the keratin network in cellular secretion. Topics: Animals; Bile; Carcinoma, Hepatocellular; Cloning, Molecular; Epidermis; Humans; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Mice; Mice, Transgenic; Microscopy, Electron; Prealbumin; Reference Values; Transfection; Tumor Cells, Cultured | 1995 |
An immunohistochemical analysis of 13 cases with combined hepatocellular and cholangiocellular carcinoma.
Thirteen cases of combined hepatocellular (HCC) and cholangiocellular carcinoma (CCC) were examined. In addition to routine pathology, immunoreactivities for carcinoembryonic antigen, alpha-fetoprotein (AFP), cytokeratin (Cam 5.2 and AE1), epithelial membrane antigen (EMA) and tumor-associated glycoprotein 72 (B72.3) were also examined. The average age of the 13 cases was 64.8 years, which lay between the average ages of pure HCC and CCC cases. They were categorized as separate type (2), collision type (6), and intermingled type (5). AE1 and EMA were the best markers to differentiate the CCC from the HCC area. B72.3 immunoreactivity was detected only in CCC (46%). There were no transitional features between HCC and CCC in two cases of the separate type and two cases of the collision type. However, focal transitional features from HCC to CCC were observed in all cases of the intermingled type and in four of six cases of the collision type. In one case of the intermingled type, many cancer cells contained both bile and mucus simultaneously, and revealed dual immunoreactivities. The conclusions are: 1) the combined type is generated from two sources; one is the intrahepatic double cancer (thoroughly separate type and a part of the collision type) and another is the stem cell origin with diverse phenotypes (intermingled type and a part of the collision tumor); and 2) AE1 was the most helpful marker to differentiate the CCC area from HCC, and other markers, e.g. AFP for HCC and EMA, CEA, and B72.3 for CCC, were also supportive but somewhat limited in the differential diagnosis. Topics: Aged; alpha-Fetoproteins; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cholangiocarcinoma; Female; Glycoproteins; Humans; Keratins; Liver; Liver Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; Neoplasms, Multiple Primary; Neoplastic Stem Cells | 1995 |
Cytokeratin patterns of liver carcinomas induced by diethylnitrosamine in monkeys.
Although the general conception is that hepatocyte- and bile duct-specific cytokeratin (CK) patterns are maintained throughout the neoplastic process, there is an increasing number of reports showing deviation from the rule. CK patterns have been found to be similar across species barriers, so it could be expected that studying the CK patterns of experimentally induced liver tumors may contribute to the elucidation of these controversies.. A CK immunohistochemical study was carried out on histologic sections from hepatocellular carcinomas (HCCs) and preneoplastic lesions from 118 monkeys chronically dosed with diethylnitrosamine (DEN), using mAbs to CK 8, CK 18, CK 7, and CK 19.. Normal monkey hepatocytes differed from human hepatocytes by displaying CK 19 in addition to the CK 8/CK 18 pairs, whereas the CK pattern of the bile duct epithelial cells was identical in monkey and human liver. In association with DEN-induced hepatocarcinogenesis, heterogeneity was observed in the CK expression, both in the HCCs and nontumorous parts of the livers. The majority of the HCC cases displayed one of the three CKs normally present in monkey hepatocytes, whereas positive expression of all three CKs (CK 8, CK 18, CK 19) and negative CK 7 was preserved in only 19.5% of the HCC cases. A so-called mixed staining pattern (negative and positive CK staining within the same tumor) was observed in approximately one-fourth of the cases. There was no correlation between the preservation of the hepatocyte-specific CK pattern and the degree of differentiation, tumor grade, or DNA ploidy of the HCCs. In approximately 10% of the primary tumors, CK 7 was expressed in the entire parenchymal cell compartment of the HCC nodules, whereas it was present in a mixed staining pattern in more than half of the cases. In lung metastases, CK 7 was less common, only expressed in approximately one-fourth of the cases. Alterations in the CK patterns were observed in the nonneoplastic hepatocytes of the tumor-bearing monkeys. These included mixed staining patterns in which the CKs appeared as positive and negative regenerating nodules side-by-side. As was observed in the HCCs, CK 7 was more commonly expressed in the nonneoplastic parenchyma in the form of mixed staining pattern than the other three CKs. Moreover, CK 7-negative HCCs occurred more frequently in CK 7-negative livers than in positive livers. Proliferation of CK 7- and CK 19-positive bile ductules and bile ductular-like (oval) cells was frequently associated with the DEN-induced liver injury and hepatocarcinogenesis.. This is the first report on CK expression in monkey liver. The findings show that the hepatocyte specific pattern is not always preserved during DEN-induced hepatocarcinogenesis and may therefore not be useful in differentiating between HCCs and cholangiocarcinomas. Topics: Animals; Antibodies, Monoclonal; Carcinoma, Hepatocellular; Chlorocebus aethiops; Diethylnitrosamine; Immunohistochemistry; Keratins; Liver Neoplasms; Lung Neoplasms; Macaca fascicularis; Macaca mulatta; Reference Values | 1995 |
A cytokeratin 8-like protein with plasminogen-binding activity is present on the external surfaces of hepatocytes, HepG2 cells and breast carcinoma cell lines.
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. Topics: Amino Acid Sequence; Breast Neoplasms; Carcinoma, Hepatocellular; Carrier Proteins; Cell Line; Cell Membrane; Female; Fluorescent Antibody Technique; Humans; Keratins; Liver; Liver Neoplasms; Membrane Proteins; Microscopy, Immunoelectron; Molecular Sequence Data; Molecular Weight; Plasminogen; Tumor Cells, Cultured | 1995 |
Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features.
We herein evaluated 36 cases of combined hepatocellular and cholangiocarcinoma (cHCC-CC) (including 29 surgically resected and seven autopsy cases) by the immunohistochemical methods of anticytokeratin antibodies 7 and 19, and then analyzed the clinicopathologic features by comparing cHCC-CC with ordinary hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The results indicated that even if mucin production could not be confirmed, nine cases with HCC areas that showed a histological resemblance to CC also showed immunohistological biliary differentiation. Therefore, we advocate that these HCC with biliary differentiation based on an immunohistochemical analysis should thus be included in the criteria of cHCC-CC in broad terms. Regardless of the extent of mucin production, the cHCC-CCs as indicated by an immunohistochemical analysis are considered to have a similar background to that of ordinary HCCs regarding such factors as the average age, male:female ratio, hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb) positivity, alpha-fetoprotein level, and the presence of cirrhosis. However, cHCC-CCs tend to metastasize to many organs and the lymph nodes, and, as a result, have a poor prognosis. Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Prognosis; Staining and Labeling; Survival Analysis | 1995 |
Bile duct-specific lectins, Dolichos biflorus agglutinin and peanut agglutinin, as probes in mouse hepatocarcinogenesis.
It is well established that alterations in the expression of cell surface glycoproteins occur during the course of tumorigenesis and can be detected immunohistochemically. However, no consistent markers of malignancy in mouse hepatocellular tumors have yet been identified.. Lectin histochemistry, using three bile duct-specific lectins, Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) and soybean agglutinin (SBA), and anti-epidermal keratin immunohistochemistry, was conducted on formalin-fixed, paraffin-embedded tissues of a spectrum of benign and malignant hepatocellular proliferative lesions of mice, including hepatocholangiocarcinomas. DBA- and PNA-binding glycoproteins in normal livers and in bile and liver tumors of mice were verified by SDS-PAGE and Western blot analysis.. Normal bile duct cells stained strongly with DBA but minimally to moderately with PNA and SBA. DBA-positive tumor cells were present in 96% of hepatocholangiocarcinomas, 89% of hepatocellular carcinomas, and 35% of hepatocellular adenomas. In comparison, 43% of hepatocholangiocarcinomas, 37% of hepatocellular carcinomas, and 24% of hepatocellular adenomas exhibited PNA staining. SBA did not specifically stain tumor cells. Normal hepatocytes and those in altered foci were consistently negative for these three lectins. Keratin-positive staining was found only in normal bile ductular cells and ductal elements in 70% of hepatocholangiocarcinomas. Electrophoresis and Western blot analysis demonstrated that, in normal livers, DBA and PNA bound to the 13- to 16-kDa and 27- to 30-kDa glycoproteins believed to be of bile duct cell origin and commonly present in hepatocellular adenomas, hepatocellular carcinomas, and hepatocholangiocarcinomas, with strongest expression in the last. In addition, hepatocholangiocarcinomas had the same high molecular mass glycoprotein (> 200 kDa) labeled with DBA as detected in bile.. Our results suggest that some malignant hepatocytes, especially in mouse hepatocholangiocarcinomas, have the potential of biliary differentiation. DBA is a sensitive marker for malignant hepatocytes in mice. Topics: Adenoma; Animals; Bile Ducts; Carcinogenicity Tests; Carcinoma, Hepatocellular; Cholangiocarcinoma; Female; Immunohistochemistry; Keratins; Lectins; Liver Neoplasms; Male; Mice; Mice, Inbred Strains; Molecular Probes; Peanut Agglutinin; Plant Lectins; Precancerous Conditions; Retrospective Studies | 1995 |
Distribution of cytokeratin 19-positive biliary cells in cirrhotic nodules, hepatic borderline nodules (atypical adenomatous hyperplasia), and small hepatocellular carcinomas.
Borderline nodule (BN) in the cirrhotic liver is considered to be a precancerous lesion leading to hepatocellular carcinoma (HCC). We investigated the distribution of cytokeratin 19 (CK 19)-positive biliary cells, recognizable by a monoclonal antibody AE1, in normal livers, chronic active hepatitis, cirrhosis, BN, and small HCC. The CK 19-positive biliary cells in the hepatic parenchyma were clearly divisible into two types (I and II). Type I cells were located within the hepatic parenchyma as small clusters forming small tubules (intraparenchymal ductules). Type II cells were bile ductules located in the peripheral rim of the hepatic lobules or hepatocellular lesions (peripheral ductular reaction) and were continuous with proliferated bile ductules in fibrous septae or portal tracts. In chronic active hepatitis and regenerative nodules of cirrhosis, a few type I cells and a variable number of type II cells were present. In the BN, all cases harbored a few type I cells as well as a variable number of type II cells. The type II cells in the BN were fewer in number and more randomly distributed than those in chronic active hepatitis and cirrhosis. Malignant foci in some BNs lacked CK 19-positive biliary cells. In small HCC, no CK 19-positive biliary cells were found; instead, AE1-positive HCC cells were present in three cases (17%). Although a great majority of type I cells corresponded to intraparenchymal ductules, some type I cells in the BN were composed of rather large tubules considered as interlobular bile ducts.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Adenoma; Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Hyperplasia; Keratins; Liver; Liver Cirrhosis; Liver Neoplasms; Precancerous Conditions | 1995 |
Immunohistochemical evaluation of canine primary liver carcinomas: distribution of alpha-fetoprotein, carcinoembryonic antigen, keratins and vimentin.
The immunohistochemical expression of the oncofetal proteins alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA), and the intermediate filament proteins keratin and vimentin was analysed in 18 canine liver carcinomas. All the tumours other than hepatocellular carcinomas, with the exception of one poorly differentiated carcinoma, were AFP negative, and only cholangiocarcinomas and mixed (hepatocellular and cholangiocellular) carcinomas were CEA positive. All the histological types of tumours expressed high and low molecular weight keratins, and keratin and vimentin were both expressed in three tumours (one moderately differentiated hepatocellular carcinoma, one mixed carcinoma and one poorly differentiated carcinoma). The findings demonstrate the use of immunohistochemical staining methods for analysing the expression of some tumour markers in routinely processed tissue samples of canine liver carcinomas, and suggest that some of the tumour markers are correlated with histological types of tumour. Topics: alpha-Fetoproteins; Animals; Antibody Specificity; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Hepatocellular; Cholangiocarcinoma; Dog Diseases; Dogs; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Sensitivity and Specificity; Vimentin | 1995 |
An autopsy case of hepatic sarcomatoid tumor: immunohistochemical comparison with a sarcomatous component of hepatocellular carcinoma.
A case of primary hepatic tumor exclusively composed of malignant cells with sarcomatous features is described and compared immunohistochemically with two cases of hepatocellular carcinoma (HCC) with a sarcomatous component. More than 30% of HCC cells were positively stained with anti-cytokeratin (CAM5.2), anti-albumin, anti-fibrinogen and anti-alpha 1-antitrypsin antibodies, and some with anti-epithelial membrane antigen. The present sarcomatoid tumor and the sarcomatous component with HCC showed similar immunohistochemistry; many tumor cells were strongly immunoreactive for vimentin and some positive for cytokeratin, albumin, fibrinogen and alpha 1-antitrypsin. Other immunohistochemical markers, indicating specific differentiations to lineage of macrophages, muscle cells, glial cells, endothelial cells and so forth, were not detected in sarcomatous tumor cells of all cases. These findings suggest that the present sarcomatoid tumor would belong to an anaplastic sarcomatous variant of HCC. Topics: Aged; Albumins; alpha 1-Antitrypsin; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Fibrinogen; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Sarcoma; Vimentin | 1994 |
Hepatocellular carcinoma metastasizing to the brain and orbit: report of three cases.
Hepatocellular carcinoma rarely metastasizes to the brain or orbit. We report 3 clinically manifest examples, one of which occurred in a 13-yr-old boy. In 2 cases the intracranial metastasis was the initial presenting lesion. The 2 cases of brain metastasis both presented with intracerebral hemorrhage. Light microscopic examination of these tumors revealed a trabecular hepatocellular carcinoma of Edmondson grade II with focal hemorrhage and necrosis. Their immunohistochemical profile was identical to that described for primary hepatocellular carcinoma. The differential diagnosis from other intracranial metastatic tumors is discussed. Topics: Adolescent; Adult; Aged; alpha 1-Antitrypsin; alpha-Fetoproteins; Brain Neoplasms; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Orbital Neoplasms | 1994 |
Expression of hepatitis B surface and core antigens and transforming growth factor-alpha in "oval cells" of the liver in patients with hepatocellular carcinoma.
Recent studies have identified epithelial cell populations in human livers that are similar to the "oval cells" and "transitional cells" seen in rat livers during the early stages of chemical carcinogenesis. It has been suggested that these cells might be precursors of hepatocytes and theoretically could be involved in hepatocarcinogenesis. The hepatitis B virus (HBV) also is believed to play a role in the etiology of hepatocellular carcinoma (HCC). Therefore, a study was conducted in nontumorous livers adjacent to HCCs obtained from 26 patients from China to determine whether HBV antigens could be identified in oval cells and transitional cells using an immunohistochemical technique. Hepatitis B surface antigen (HBsAg) was detected in the nontumorous livers of 22/26 (85%) patients. HBsAg was detected in oval cells in 18/26 (69%), in transitional cells in 21/26 (81%), and in mature hepatocytes in 22/26 (85%), but not in bile duct or ductule cells. Transforming growth factor-alpha (TGF-alpha) was expressed in oval cells, transitional cells, and bile duct cells in 24/26 (92%) patients, an in mature hepatocytes in 25/26 (96%). Coexpression of HBsAg and TGF-alpha was identified in the same cells in populations of oval cells and transitional cells of selected patients. Because of the possibility that oval cells could be a source of evolving HCC, these findings suggest that expression of TGF-alpha associated with HBV infection of oval cells could be a mechanism of human hepatocarcinogenesis. Thus, oval cells could be a site (or one of the sites) where HBV participates in the development of HCC. Topics: Adult; Aged; Carcinoma, Hepatocellular; Epithelium; Female; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Transforming Growth Factor alpha | 1994 |
Could the cytokeratin molecule be modulated during tumor transformation in hepatocellular carcinoma?
The stability of cytokeratin during tumor transformation in hepatocellular carcinoma was studied. We applied biochemical methodology to look into the switching of cytokeratin molecules in tumor transformation. First, by centrifugation the cytokeratin molecules were extracted from both liver and hepatoma tissues. The extracts were then soaked with cyanogen bromide-activated Sepharose 4B beads previously coated by monoclonal anti-cytokeratin antibody. The bound molecules were then released from the resin with salt. Second, the isolated molecules of both were treated with lysosomal enzyme and analyzed on two-dimensional gels. The results demonstrated that there was a modulation in cytokeratin molecules, and the hepatoma cytokeratin was generated from the hepatocyte cytokeratin. Topics: Blotting, Western; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Liver; Liver Neoplasms; Peptide Mapping; Precipitin Tests | 1994 |
Intermediate filament reactivity in hyperplastic and neoplastic lesions from medaka (Oryzias latipes).
To determine if hyperplastic and neoplastic lesions from medaka showed similar immunoreactivity to intermediate filament antibodies as the tissues of origin, two week old medaka were exposed to 10 or 20 mg/L of methylazoxymethanol acetate for two hours and transferred to clean water for up to six months. Using a streptavidin peroxidase method, paraffin embedded Bouins fixed neoplasms were incubated with cytokeratin, vimentin, or neurofilament antibodies. Like their nonneoplastic cellular counterparts, hepatocellular carcinoma, pancreatic acinar carcinoma and mesenchymal neoplasms including hemangioma and hemangiopericytoma reacted negatively to cytokeratin antibodies. Cholangiocarcinoma, mesothelioma, and proliferative lesions containing biliary epithelial cells reacted positively to cytokeratin antibodies. All neoplasms and proliferative lesions were negative with vimentin and neurofilament antibodies. These data indicate that while some epithelial neoplasms showed cytokeratin reactivity similar to the parent tissues, additional markers are needed to identify mesenchymal tissues and neoplasms. Topics: Adenoma, Liver Cell; Animals; Antibodies; Carcinogens; Carcinoma, Acinar Cell; Carcinoma, Hepatocellular; Cell Division; Cholangiocarcinoma; Hemangioma; Hemangiopericytoma; Hyperplasia; Immunohistochemistry; Intermediate Filaments; Keratins; Liver; Liver Neoplasms; Methylazoxymethanol Acetate; Neurofilament Proteins; Oryzias; Pancreas; Pancreatic Neoplasms; Vimentin | 1994 |
Immunohistochemical detection of breast specific antigens and cytokeratins in metastatic breast carcinoma in the liver.
The present study was performed to evaluate the diagnostic reliability of antibodies to breast carcinoma-specific antigen and antibodies to cytokeratin catalogue in a metastatic hepatic lesion. Immunohistochemical examinations using antibodies to gross cystic disease fluid protein-15 (GCDFP-15), BCA-225 (a glycoprotein secreted by T47D breast carcinoma cell line) and BRST-5 (a glycoprotein identified in SK-BR-7 breast carcinoma cell line), anti-cytokeratin monoclonal antibodies of MA904, AE3, CAM5.2, PKK1 and cytokeratin 19, and polyclonal anti-keratin antibodies were done. These were on 15 cases of primary breast carcinoma, eight cases of metastatic breast carcinoma in the liver, five cases of cholangiocarcinoma, eight cases of hepatocellular carcinoma and 11 cases of metastatic adenocarcinoma of another primary tumor in the liver. Results showed that GCDFP-15 antigen was most reliable: it was 100% positive in both primary and metastatic breast carcinomas unrelated to histological subtypes, and 100% negative in primary or other metastatic carcinomas in the liver. BCA-225 antigen was detected in high amounts in breast carcinomas (100%, 23/23), but it was positive in cholangiocarcinomas (80%, 4/5) and another metastatic carcinoma in the liver (64%, 7/11). BRST-5 was specifically positive in breast carcinomas but the positivity was low (13%, 3/23). Cytokeratin 19 and keratin were useful to discriminate hepatocellular carcinomas (0%, 0/8) from breast carcinomas (87%, 20/23; 96%, 22/23), but they were also positive in cholangiocarcinomas (100%, 5/5) and other metastatic carcinomas in the liver (91%, 10/11).(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Apolipoproteins; Apolipoproteins D; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Carrier Proteins; Cholangiocarcinoma; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Transport Proteins; Middle Aged | 1993 |
Comparative immunohistochemical study of primary and metastatic carcinomas of the liver.
Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas. Topics: Adenocarcinoma; Adenoma, Bile Duct; alpha-Fetoproteins; Antibodies, Monoclonal; Antigens, Differentiation, Myelomonocytic; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Membrane Glycoproteins; Mucin-1; Retrospective Studies | 1993 |
Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis.
Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma. Topics: Adult; alpha-Fetoproteins; Carcinoma, Hepatocellular; Cell Division; Female; Hepatitis B; Humans; In Situ Hybridization; Keratins; Liver; Liver Neoplasms; Male; Middle Aged; Serum Albumin | 1992 |
Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma.
The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case. Topics: Adrenal Cortex Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Diagnosis, Differential; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Liver Neoplasms | 1992 |
Primary culture of liver cancer tissues with or without transcatheter arterial embolization and establishment of a cell strain.
More epithelial-like cells are found in primary cultures of transcathetel arterial embolization (TAE)-untreated human liver cancer tissues than in those of TAE-treated tissues. A new cell strain, HUH-33, established from the former, grows slowly and is untransplantable into nude mice and secretes alpha-fetoprotein, albumin and some other tumor markers. Chromosome numbers are widely distributed. HUH-33 expresses hepatocyte type keratin and contains desmosome- or intermediate filament bundle-like structures. Topics: Aged; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Line; Desmosomes; Embolization, Therapeutic; Female; Humans; Immunohistochemistry; Intermediate Filaments; Karyotyping; Keratins; Liver Neoplasms; Male; Middle Aged; Tumor Cells, Cultured | 1992 |
[A case of lung cancer with Mallory bodies].
This paper is a report of a large cell carcinoma (solid carcinoma with mucus formation-WHO) which developed in the right upper lobe of a 71-year-old woman and in which cytoplasmic Mallory body-like inclusions (MBL) similar to Mallory bodies (MB) often found in alcoholic liver disease and hepatocellular carcinoma were noted in the tumor cells. MBL was an eosinophilic massive or reticular hyalin, and showed staining properties similar to those of MB in general stainings. Electron microscopically, it was made up mainly of a fine granular amorphous substance with high electron density and was not surrounded by a membrane. A part of the margin was in close contact with filaments approximately 10 nm in diameter, with tonofibril-like structures around it, which suggested a relationship with cytokeratin. On immunoperoxidase staining using a couple of cytokeratin antibodies, definitely positive findings were not obtained with MBL themselves. MBL of this case basically has the same character as that of MBL which appears in fibrous lesions in the lung and MB in liver disease. It was concluded that it is necessary to preoperatively distinguish this entity cytologically or histologically from pulmonary metastasis of hepatocellular carcinoma. Topics: Aged; Carcinoma, Hepatocellular; Carcinoma, Small Cell; Diagnosis, Differential; Female; Humans; Inclusion Bodies; Keratins; Liver Neoplasms; Lung Neoplasms | 1992 |
Polymeric Ig receptor expression in hepatocellular carcinoma.
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. Topics: Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Humans; Keratins; Liver; Liver Neoplasms; Membrane Glycoproteins; Receptors, Immunologic; Secretory Component | 1992 |
Co-ordinate expression of c-fos, p53 and cytokeratin genes during the alteration of growth of human hepatoma cells. mRNA levels measured by reverse transcription and polymerase chain reaction.
Teleocidin, a tumor promoter, inhibited the proliferation, enhanced cytokeratin assembly and increased the type III procollagen production of PLC/PRF/5 hepatoma cells. Teleocidin transiently increased the levels of c-fos and p53 mRNAs measured by reverse transcription and polymerase chain reaction. This was followed by a reduction of c-myc mRNA and an increase of cytokeratin mRNA. The level of p120 mRNA was not remarkably altered. Sequential alterations of the expression of c-fos, p53, c-myc and cytokeratin genes induced by teleocidin may be responsible for the morphological and functional changes of hepatoma cells induced by this tumor promoter. Topics: Base Sequence; Carcinoma, Hepatocellular; Gene Expression; Genes, fos; Genes, myc; Genes, p53; Humans; Keratins; Liver Neoplasms; Lyngbya Toxins; Molecular Sequence Data; Polymerase Chain Reaction; RNA-Directed DNA Polymerase; RNA, Messenger; Tumor Cells, Cultured | 1992 |
Vacuole formation and cytokeratin rearrangement of hepatoma cells induced by teleocidin are not associated with down-regulation of protein kinase C.
PLC/PRF/5 human hepatoma cells cultured with teleocidin reduced the rate of cell proliferation and were transformed into large cells with many vacuole-like subcellular structures. In these vacuolated cells, the protein content per cell increased without changing the total cellular protein synthesis. Cytokeratin was one of the proteins which increased quantitatively. This intermediate filament formed fibrous network structures throughout the enlarged cytoplasm. The assembly of other cytoskeletal proteins such as actin, tubulin, and vimentin was not altered remarkably, suggesting that teleocidin morphologically transformed the hepatoma cells by changing the assembly of cytokeratin protein selectively. On the other hand, the alterations of cell proliferation, cell morphology, and cytokeratin assembly induced by teleocidin were not associated with either down-regulation of protein kinase C or reduced number of epidermal growth factor receptors. In addition, these teleocidin effects were not mimicked by the protein kinase C agonist 1-oleoyl-2-acetylglycerol or inhibited by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. From these results it can be speculated that the morphological transformation and reduced cell proliferation induced by teleocidin may be mediated by still unknown mechanisms unrelated to protein kinase C. Topics: Carcinoma, Hepatocellular; Cell Division; Cell Line; Cell Membrane; Cytoskeletal Proteins; Cytosol; DNA, Neoplasm; Humans; Keratins; Kinetics; Liver Neoplasms; Lyngbya Toxins; Molecular Weight; Neoplasm Proteins; Nuclear Proteins; Protein Kinase C; Vacuoles | 1991 |
An immunohistochemical study of sarcomatoid liver carcinomas.
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. Topics: Aged; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Fibrosarcoma; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Leiomyosarcoma; Liver Neoplasms; Male; Middle Aged; Sarcoma; Vimentin | 1991 |
Well-differentiated hepatocellular carcinoma associated with long-term survival. Report of two cases.
Two cases of well-differentiated hepatocellular carcinoma (HCC) with focal biliary differentiation are presented. The distinct histological features of these neoplasms and the unusually protracted clinical course of 8 and 10 years distinguish them from previously described pathological categories of primary hepatic tumors. Electron microscopic and immunohistochemical findings support a dual hepatic and bile duct differentiation of the tumor cells. If additional examples of this tumor are found to be associated with a similarly prolonged symptom-free survival, the distinction of this entity from traditional, rapidly fatal HCC becomes important. Less aggressive therapeutic options may be entertained. Topics: Adult; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Bile Ducts; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Chorionic Gonadotropin; Chromogranins; Female; Hepatic Duct, Common; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Phosphopyruvate Hydratase; Prognosis; Time Factors; Vimentin | 1991 |
Immunocytochemistry of cytokeratins in primary human liver tumors.
Human liver parenchymal cells have a very simple cytokeratin composition and express only one cytokeratin pair: cytokeratin 8 (a type II cytokeratin, molecular weight 52 kD) and cytokeratin 18 (a type I cytokeratin, molecular weight 45 kD). Intrahepatic bile duct cells contain in addition to cytokeratins 8 and 18 also cytokeratins 7 (a type II cytokeratin, molecular weight 54 kD) and cytokeratin 19 (a type I cytokeratin, molecular weight 40 kD). The paper deals with the cytokeratin expression in various types of benign and malignant primary liver tumors as assessed by immunohistochemical methods or by the use of gel electrophoresis and immunoblotting of cytoskeletal extracts. Topics: Adenoma, Bile Duct; Biomarkers; Carcinoma, Hepatocellular; Histocytochemistry; Humans; Hyperplasia; Keratins; Liver Diseases; Liver Neoplasms | 1991 |
Novobiocin modulates cytokeratin assembly and differentiation of human hepatoma cells induced by butyrate and teleocidin.
A differentiation inducer butyrate and a tumor promoter teleocidin had inhibitory effects on the proliferation of PLC/PRF/5 hepatoma. Both of these reagents stimulated the production of procollagen type III peptide, enhanced the cytokeratin assembly and altered the morphological appearance. Novobiocin, a topoisomerase II inhibitor, enhanced the cytokeratin assembly induced by butyrate but antagonized that induced by teleocidin without changing the expression and the phosphorylation state of cytokeratin proteins. In addition, novobiocin acted synergistically with butyrate but not with teleocidin in stimulating the procollagen production and the acetate uptake. These results suggest that butyrate and teleocidin induce cell differentiation via distinct signaling pathway and that novobiocin and butyrate can be used as subsidiary drugs in preventing the growth of hepatoma. Topics: Acetylation; Butyrates; Butyric Acid; Carcinogens; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cytoskeletal Proteins; Drug Synergism; Humans; Keratins; Liver Neoplasms; Lyngbya Toxins; Novobiocin; Peptide Fragments; Procollagen; Tumor Cells, Cultured | 1991 |
A cytokeratin-immunohistochemical study of hepatoblastoma.
Six cases of hepatoblastoma (five epithelial, one mixed epithelial-mesenchymal) were studied on serially cut cryostat sections, using a panel of monoclonal antibodies directed against individual cytokeratins, vimentin, and desmin, in an indirect immunoperoxidase procedure. Embryonic and fetal-type tumor cells expressed the "hepatocellular" cytokeratins no. 8 and 18 but, surprisingly, also expressed the "bile duct type" cytokeratin no. 19. In addition, two cases had a number of tumor cells which were also positive for the "bile duct type" cytokeratin no. 7. Cells embedded in osteoid-like material were immunoreactive for vimentin but also for cytokeratins no. 7, 18, and 19. Gel electrophoresis, and Western blotting of cytoskeletal extracts, confirmed the immunohistochemical data. The implications of these findings for the histogenesis of hepatoblastoma are discussed in this report. Topics: Adolescent; Adult; Blotting, Western; Carcinoma, Hepatocellular; Child; Child, Preschool; Desmin; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immunohistochemistry; Infant; Keratins; Liver Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; Vimentin | 1990 |
Growth-factor independence of a new differentiated hepatitis B virus DNA-negative human hepatoma cell line.
The establishment of a new, differentiated, hepatitis B virus DNA-negative, human hepatoma cell line (named PLC/AN/2) is described. Neoplastic liver tissue was obtained during hepatectomy in an HBsAg-negative man. The established cell line is negative for alpha-fetoprotein and carcinoembryonic antigen; it has retained in vitro some of the differentiated functions of normal hepatocytes. Additionally, it presents a distinctive rearrangement (translocation) at the long arm of chromosome 4. The high degree of independence from serum growth factor requirements appears to be a major in vitro characteristic of PLC/AN/2 cells, making them a suitable model system for the more precise definition of the human hepatocellular carcinoma phenotype, including mechanisms of growth control. Topics: Carcinoma, Hepatocellular; Cell Differentiation; Cell Division; Culture Media; DNA, Viral; Growth Substances; Hepatitis B virus; Humans; Karyotyping; Keratins; Liver Neoplasms; Male; Middle Aged; Molecular Weight; Translocation, Genetic; Tumor Cells, Cultured | 1990 |
Mixed hepatoblastoma in the adult: morphological and immunohistochemical findings.
A case of mixed hepatoblastoma in a 66-year-old man is discussed. Assessment of malignant mesenchymal and malignant epithelial elements yields the diagnosis. In the reported case, the epithelial area consisted of fetal hepatocytes. Distinct ductal differentiation, chondroid and even asteoid metaplasia were recorded. The morphological and immunohistochemical findings observed in the given patient are compared with data published in the world literature. Topics: Aged; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male | 1990 |
Abundant expression of cytokeratin 7 in fibrolamellar carcinoma of the liver.
Two cases of fibrolamellar carcinoma of the liver, one with lymph node metastasis are reported. Using immunohistochemistry as well as one- and two-dimensional gel electrophoresis and Western blotting, tumour cells of both primary lesions and of the metastasis were found to express cytokeratin polypeptides 8 and 18 and, surprisingly, cytokeratin 7. A small number of cells also expressed cytokeratin 19. This is the first detailed analysis of the cytokeratin expression of fibrolamellar carcinoma, and is also the first to present biochemical evidence that, contrary to what has been suggested, hepatocellular carcinomas do not always preserve the pattern of cytokeratin expression of normal hepatocytes. Topics: Carcinoma, Hepatocellular; Child; Humans; Immunoblotting; Immunohistochemistry; Keratins; Liver Neoplasms; Lymphatic Metastasis; Male | 1990 |
[A hepatocellular carcinoma showing sarcomatous features and an extensive metastasis].
A 47-year-old female was admitted for a right hypochondrial pain and was diagnosed as having a hepatic tumor with a cystic lesion. After a right and a caudal lobectomy, she died of hepatic failure due to a tumoral recurrence. At autopsy, a cystic tumoral nodule, 15 x 7 cm in size, and numerous other nodules were revealed in the liver. Metastases were seen in both lungs, the left kidney, the colon, the mesenterium, the peritoneum, the diaphragm, and the para-pancreatic lymph nodes. The hepatic tumors consisted of four types of tumor cells: spindle, round, mixed (spindle and round cells), and cells with pseudoalveolar features. All tumor cells showed a positive immunohistochemical reaction to polyclonal keratin, low molecular monoclonal keratin, alpha 1 anti-trypsin, vimentin and to actin in their cytoplasms. This is considered a very rare case. Topics: Actins; alpha 1-Antitrypsin; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Sarcoma; Vimentin | 1990 |
Cytokeratin expression in human cell lines derived from liver tumors.
Immunohistochemical staining of cell lines derived from human liver tumours showed that five cell lines derived from hepatocellular carcinoma (HCC) and hepatoblastoma were stained positively with monoclonal keratin antibodies, CK-5 (Ker-18-specific) and KL-1 (broad specificity), but not with CK-7 (Ker-7-specific). On the other hand, four carcinoma cell lines derived from the biliary system were stained positively with not only CK-5 and KL-1, but also CK-7. Topics: Albumins; Alkaline Phosphatase; alpha-Fetoproteins; Antibodies, Monoclonal; Bile Duct Neoplasms; Biomarkers, Tumor; Carcinoma; Carcinoma, Hepatocellular; Gallbladder Neoplasms; Humans; Keratins; Liver Neoplasms; Neoplasm Proteins; Tumor Cells, Cultured | 1990 |
Expression of cytokeratins in normal and diseased livers and in primary liver carcinomas.
Hepatocytes and bile duct epithelium express several types of cytokeratins, the characteristic intermediate-filament proteins of epithelial cells. The cytokeratin antigen expression was studied in normal and diseased livers, intrahepatic cholangiocarcinomas, and hepatocellular carcinomas by immunohistochemical methods using a panel of polyclonal and monoclonal antibodies to cytokeratins. Ten percent formaldehyde solution-fixed, paraffin-embedded sections obtained from ten patients without liver disease, 18 patients without liver disease, 18 patients with different stages of primary biliary cirrhosis, 14 patients with alcoholic hepatitis, ten patients with fatty liver hepatitis secondary to diabetes mellitus or morbid obesity, five patients with hepatocellular carcinomas, and five patients with cholangiocarcinomas were examined. The results suggested that hepatocytes and bile duct epithelium retain their distinct cytokeratin profiles in liver disease, including malignant transformation. Therefore, demonstration of cytokeratins in the liver is useful in establishing the cellular origin of neoplasms and understanding the pathogenesis of liver diseases. Topics: Adenoma, Bile Duct; Carcinoma, Hepatocellular; Fatty Liver; Hepatitis; Humans; Keratins; Liver; Liver Cirrhosis, Biliary; Liver Diseases; Liver Neoplasms; Reference Values; Tissue Distribution | 1989 |
Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma.
Hepatocellular carcinoma may share histologic features with a wide variety of epithelial tumors. To facilitate its pathologic diagnosis, clinical and pathologic material was reviewed from 62 patients with hepatocellular carcinoma and immunostaining was performed with polyclonal anti-carcinoembryonic antigen (pCEA), monoclonal anti-carcinoembryonic antigen (mCEA), anti-epithelial membrane antigen (EMA), and an antikeratin (KER AE1/AE3). Clinical information and follow-up were available for all patients from several sources. Cases with ambiguous clinical data or findings suggestive of metastatic carcinoma to the liver were excluded. In addition, the following tumors were immunostained and compared to hepatocellular carcinoma: 10 cholangiocarcinomas; 14 pancreatic adenocarcinomas; 4 gastric adenocarcinomas; 3 breast carcinomas; 5 renal carcinomas; 3 combined germ cell tumors of the testis; 3 adrenal cortical carcinomas; and 4 melanomas. The pCEA stained bile canaliculi in normal liver and in 39 of 62 (63%) hepatocellular carcinomas. This canalicular staining pattern of pCEA was unique to hepatocellular carcinoma. The mCEA (1 of 62, 1.6%) was almost always negative, and KER AE1/AE3 (9 of 59, 15.3%) was occasionally positive. The EMA stained 25 of 62 (40.3%). The adrenal cortical carcinomas and melanomas were negative for all antigens except rare pCEA and focal EMA staining in an adrenal tumor. Other carcinomas showed cytoplasmic pCEA (36 of 44, 81.8%), mCEA (40 of 46, 87.7%), EMA (41 of 43, 95.4%), and KER AE1/AE3 (42 of 44, 95.5%). Canalicular staining with pCEA is specific for hepatocellular carcinoma, while negativity with mCEA and KER AE1/AE3 is suggestive of hepatocellular differentiation. Topics: Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Liver Neoplasms; Membrane Glycoproteins; Mucin-1 | 1989 |
Immunocytochemical evaluation of liver fine-needle aspirations.
A panel of antibodies to intermediate filaments, oncofetal antigens, and hepatocellular markers was tested on a prospective series of liver fine-needle aspirates to determine its utility in distinguishing hepatocellular carcinoma (HCC) from metastatic carcinomas. All fine-needle aspirations were assisted to ensure adequate cellularity, and were examined by a multimodal approach that included the preparation of B-5-formaldehyde-fixed cell blocks by the plasmathrombin technique. alpha-Fetoprotein was positive in four of eight HCCs, including the one example of combined hepatocellular-cholangiocarcinoma, but negative in the one case of pure cholangiocarcinoma and all cases of metastatic carcinoma. Carcinoembryonic antigen positivity was noted in four HCCs, a high proportion of metastatic adenocarcinomas, and occasional metastatic squamous cell carcinomas, but not in the one example of cholangiocarcinoma. Hepatitis B surface antigen was positive in only two cases of HCCs, but not in any metastatic tumors. Keratin and vimentin were positive, respectively, in four and three HCCs, and a variable proportion of metastatic carcinomas often coexpressed both antigens. Epithelial membrane antigen was positive in five of the eight HCCs. Our findings are consistent with the view that alpha-fetoprotein and hepatitis B surface antigen are reliable markers for HCC. However, none of the immunocytochemical markers reliably distinguished the primary site of metastatic carcinoma. The intensity of the immunostains in the fine-needle aspirations was comparable with that observed in tissues, but fragmentation of cell groups interfered with interpretation. Multiple passes and verification of the cellularity of the aspirates are crucial factors for the success of this approach to diagnosis. Topics: alpha 1-Antitrypsin; alpha-Fetoproteins; Biopsy, Needle; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Evaluation Studies as Topic; Humans; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Microscopy, Electron; Vimentin | 1989 |
[An immunohistochemical study on primary carcinoma of the liver].
Using 109 hepatocellular carcinomas (HCG), 34 cholangiocellular carcinomas (CCC), 4 mixed hepatocellular-cholangiocellular carcinomas (MHC) and 24 metastatic adenocarcinomas in the liver (MA), an immunohistochemical study on primary carcinoma of the liver was performed by means of the ABC method for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), tissue polypeptide antigen (TPA) and keratin. The material consisted of surgical specimens of Kosin Medical College including 50 HCC, 17 CCC and 1 MHC, surgical specimens of 20 HCC from the University of Occupational and Environmental Health, Japan (UOEH) and autopsied specimens from UOEH that included 39 HCC, 17 CCC, 3 MHC and 24 MA. All the specimens were fixed with 10-15% formalin and embedded in paraplast manually at Kosin Medical College and by utilizing an automatic embedding machine with a decompressing procedure at UOEH. The antigenicity of TPA and keratin was preserved better in the specimens of Kosin Medical College than in those from UOEH. It is therefore assumed that manually embedded specimens are superior to specimens embedded by using an embedding machine with regard to the preservation of some antigenicities. The immunoreactivity of the 4 antigens in CCC cells was significantly higher than that in HCC cells, and the intracellular localization of antigens generally showed several characteristics in HCC and CCC. However, as the same localization of antigens is also seen in both HCC cells and CCC cells, it is considered that the immunohistochemical examination using plural antibodies is not always useful for a differential diagnosis between HCC and CCC, which is difficult in conventional sections. That TPA in HCC may be an oncodevelopmental antigen is suggested by the facts that the higher the grade of HCC, the higher the immunoreactivity of HCC cells, that hepatocytes with possible higher activity sometimes showed a positive reaction in the present study and that TPA is expressed in fetal hepatocytes in a fetus up to 20 weeks in the literature. Topics: Adenoma, Bile Duct; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Peptides; Tissue Polypeptide Antigen | 1989 |
The diagnostic utility of the keratin profiles of hepatocellular carcinoma and cholangiocarcinoma.
A total of 32 hepatocellular carcinomas (HCC), 10 cholangiocarcinomas (CC), one combined HCC-CC, and 10 adenocarcinomas metastatic to the liver were studied immunohistochemically using AE1 and Cam 5.2, monoclonal antikeratin antibodies with different specificities. AE1 recognizes keratins with molecular weights of 56.5, 50/50', 48, and 40 kd (keratin nos. 10, 14, 15, 16, and 19, according to Moll's catalog), and labels many epithelia, including bile duct epithelium, but not hepatocytes. Both biliary epithelium and hepatocytes are stained by Cam 5.2, which reacts with keratins of molecular weights 50, 43, and 39 kd (corresponding to keratin nos. 8, 18, and 19). Tissues were formalin fixed, paraffin embedded, and a three-stage immunoperoxidase technique was employed. Of 32 pure HCCs, 29 were unreactive with AE1 yet were positive with Cam 5.2. The intensity and extent of immunostaining with Cam 5.2 did not correlate with tumor grade. In contrast to the HCCs, all 10 CCs and the 10 hepatic metastases were strongly positive with both AE1 and Cam 5.2. The combined HCC-CC was also labeled by both antibodies. We conclude that most HCCs express an immunohistochemical keratin profile identical to that of nonneoplastic hepatocytes, which differs from the keratin patterns of bile ducts, CCs, and metastatic adenocarcinomas from a variety of primary sites. These differences in immunoreactivity with antikeratin antibodies may prove useful in diagnostic surgical pathology. Topics: Adenoma, Bile Duct; Bile Duct Neoplasms; Carcinoma, Hepatocellular; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Neoplasm Staging | 1988 |
Cytokeratin expression in hepatocellular carcinoma: an immunohistochemical study.
Normal human hepatocytes express cytokeratins no. 8 and 18, whereas bile duct cells contain the same cytokeratins and, in addition, cytokeratins no. 7 and 19. This cytokeratin pattern is believed to be preserved during neoplastic transformation. Thirty-four cases of hepatocellular carcinoma (11 well differentiated, 16 moderately differentiated, 7 poorly differentiated) were studied on frozen sections using monoclonal antisera directed against individual cytokeratins no. 7, 8, 18, and 19 in an immunoperoxidase procedure. In 17 of 34 cases, tumor cells showed only reactivity with monoclonals anticytokeratin no. 8 and 18. However, 17 of 34 cases showed an aberrant pattern in that a variable number of tumor cells were stained with anticytokeratins no. 7 and/or 19 in addition to no. 8 and 18. Only three of 11 well-differentiated cases displayed an unexpected cytokeratin pattern, whereas an aberrant pattern was present in all seven of seven poorly differentiated cases. These results are in conflict with previously published data obtained by two-dimensional gel electrophoresis and immunohistochemistry. They indicate that the cytokeratin pattern might not always be preserved during neoplastic transformation. The implication of this finding for the differential diagnosis of metastatic gastrointestinal carcinomas is discussed. Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged | 1988 |
Combined hepatocellular-cholangiocarcinoma with variable sarcomatous transformation.
An adult case of combined hepatocellular-cholangiocarcinoma with variable sarcomatous changes is presented. Histologically, the tumor was composed of hepatocellular carcinoma, cholangiocarcinoma, and sarcomatous portions, including spindle-shaped, pleomorphic, and osteoplastic varieties. There was a transitional cell form between the carcinoma and sarcomatous cells. These tumor elements showed both independent and concurrent metastases. Immunohistochemical examination for keratin revealed positive staining in the tumor cells except for osteoplastic immature cells, whereas vimentin had positive results only in some sarcomatous cells. On the basis of these findings, the possibility of sarcomatous transformation of combined hepatocellular-cholangiocarcinoma was discussed. Topics: Adenoma, Bile Duct; Aged; Carcinoma, Hepatocellular; Gastric Mucosa; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Lymph Nodes; Male; Neoplasm Metastasis; Sarcoma; Vimentin | 1988 |
An unusual hepatocellular carcinoma: an ultrastructural and immunohistochemical study.
This paper describes a 50-year-old woman with an unusual malignant tumour of the liver. Poorly differentiated liver cells, tubular structures and spindle cells in abundant intercellular ground substance characterized the tumour. Extremely high serum concentration of alpha-fetoprotein was present. The spindle cells showed strong immunoreactivity against this antigen and vimentin. Both the spindle and epithelial cells showed negative immunoreactivity against desmin, epithelial membrane antigen and keratin. Markers for low molecular cytokeratin (MAK-6, CAM 5.2) were demonstrated in both cell types. Ultrastructurally the neoplastic epithelial cells showed frequent intercellular spaces and well-formed brush borders suggestive of differentiation towards hepatocytes and bile duct epithelium. The immunohistological findings established the epithelial nature of the spindle cells thus distinguishing the tumour from hepatoblastoma. Topics: alpha-Fetoproteins; Carcinoma, Hepatocellular; Desmin; Female; Humans; Keratins; Liver Neoplasms; Middle Aged | 1988 |
Distinction between hepatocellular carcinoma, cholangiocarcinoma, and metastatic carcinoma based on immunohistochemical staining for carcinoembryonic antigen and for cytokeratin 19 on paraffin sections.
An antiserum to carcinoembryonic antigen (CEA) and a monoclonal antibody to cytokeratin 19 (CK 19) were studied for their suitability as diagnostic reagents for the differential diagnosis of primary and secondary malignant epithelial tumours of the liver, on paraffin sections. With the antiserum to CEA, positive bile canalicular structures were found in 60 per cent of the hepatocellular carcinomas. All the cholangiocarcinomas and 66.6 per cent of the metastatic carcinomas were positive for CEA, without displaying a canalicular staining pattern. All the hepatocellular carcinomas were negative for CK 19. All the cholangiocellular carcinomas and the metastatic carcinomas were positive for CK 19. This staining profile may prove helpful in difficult diagnostic cases. Topics: Adenocarcinoma; Adenoma, Bile Duct; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Keratins; Liver Neoplasms | 1988 |
Evidence for a hepatocellular lineage in a combined hepatocellular-cholangiocarcinoma of transitional type.
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. Topics: Adenoma, Bile Duct; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratins; Liver; Liver Cirrhosis; Liver Neoplasms | 1988 |
[Comparative studies of intermediate filament patterns and components in human hepatoma cells and HeLa cells].
Topics: Carcinoma, Hepatocellular; Cytoskeleton; HeLa Cells; Humans; Intermediate Filaments; Keratins; Liver Neoplasms; Vimentin | 1988 |
Hepatocellular carcinoma with sarcomatous change. Clinicopathologic and immunohistochemical studies of 14 autopsy cases.
Among 355 autopsy cases of hepatocellular carcinoma (HCC), 14 cases exhibited sarcomatous appearance (incidence, 3.9%). A clinicopathologic study was performed in these 14 cases, and the immunohistochemical localization of keratin (KRT), vimentin (VMT), albumin (ALB), fibrinogen (FBG) and alpha-fetoprotein (AFP) was also examined using the avidin-biotin complex method. Clinically, the HCCs with sarcomatous appearance were characterized by negative or low serum AFP levels and high incidence of extrahepatic metastasis. Grossly they were of infiltrative, mixed expansive and infiltrative, and pedunculated types. Histologically, the tumor consisted mainly of spindle-shaped cells and partly of multinucleated cells, and showed a sinusoidal growth pattern at the tumor-nontumor boundary. Immunohistochemically, tumor cells in the regions showing sarcomatous appearance were frequently found to be positive to KRT and VMT, whereas the percentage of positivity to ALB, FBG, and AFP were not significantly different from those in ordinary HCC. These results strongly suggest that the lesion showing sarcomatous appearance represents the sarcomatous change of HCC rather than being regarded as the complication of HCC and sarcoma. Topics: Adult; Aged; Albumins; alpha-Fetoproteins; Carcinoma, Hepatocellular; Fibrinogen; Hepatitis B Surface Antigens; Histocytochemistry; Humans; Keratins; Liver Neoplasms; Middle Aged; Sarcoma; Time Factors; Vimentin | 1987 |
Keratin polypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects.
Five monoclonal antibodies recognizing different keratin polypeptides in immunoblotting or different epithelial cell types in complex tissues were studied for their suitability as reagents for the differential diagnosis of primary and secondary malignant epithelial liver tumors. The broad specificity keratin antibodies lu-5 and KL-1 stained all epithelial liver neoplasms. In contrast the antibodies CK-7 (Ker-7-specific), CK-2 (Ker-18-specific) and KA-4 (Ker-19-specific in liver) allow these neoplasms to be divided into three groups: Hepatocellular carcinomas were CK-2-positive and CK-7-negative. Cholangiocellular carcinomas, liver metastases of extrahepatic bile duct carcinomas, liver metastases of a ductal carcinoma of breast, and a follicular thyroid carcinoma were stained positively by CK-2, CK-7, and KA-4. In 1 of 6 hepatocellular carcinomas neoplastic hepatocytes were focally labeled by KA-4. In a focal nodular hyperplasia of the liver modified hepatocytes were decorated not only by CK-2 but also by CK-7 and KA-4. Liver metastases of colorectal adenocarcinomas and of a carcinoid tumor were stained positively by CK-2 and KA-4 but not by CK-7. Topics: Adenoma, Bile Duct; Antibodies, Monoclonal; Antibody Specificity; Bile Ducts; Carcinoma, Hepatocellular; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms | 1987 |
Hepatic adenoma within a spindle cell carcinoma in a woman with a long history of oral contraceptives.
The case of a young woman is presented who had a long history of oral contraceptive use and who was found to have a focal hepatic adenoma within a large spindle cell carcinoma of the liver. The pleomorphic tumor is positive for keratin and alpha 1-antitrypsin by immunohistochemistry, has intracellular lumina by electron microscopy, a moderately high thymidine labeling index, and is negative for estrogen and progesterone receptors. A review of the literature concerning liver tumors occurring in young patients indicates that there is an underlying disturbance of the hormonal milieu in all instances reported. The prognosis is widely variable and unpredictable.. Clinical and laboratory evidence of an association of oral contraceptive (OC) use with the subsequent development of benign and malignant hepatobiliary neoplasia is growing. The authors present a case in which an adenoma within a large, multicentric anaplastic spindle cell carcinoma occurred in a woman with a long history of OC use. The patient, a 38-year-old gravida 2, para 2, was diagnosed following low-grade fevers and right upper quadrant pain. A partial hepatectomy was performed with no complications; however, a follow-up examination 2 months later revealed widespread intra-abdominal tumor recurrence histologically identical to the original tumor. Immunostaining for alpha 1 antitrypsin and keratin was strongly positive in tumor cells, indicating a biliary derivation. Electron microscopy indicated an epithelial derivation as well, including the presence of intracellular lumens, intermediary filaments, and numerous intercellular junctions. Estrogen and progesterone receptors were negative in the tumor. The tritiated thymidine labeling index was 5.05%, with an estimated potential doubling time of 11 days. This woman had no history of hepatitis, no family or personal history of neoplasms, and no known hepatotoxin exposure. The only medication used by the patient was Norlestrin, an OC containing 1 mg norethindrone and 50 mcg ethinyl estradiol that she had taken continuously for the past 8 years. Topics: Adult; alpha 1-Antitrypsin; Biopsy, Needle; Carcinoma; Carcinoma, Hepatocellular; Contraceptives, Oral, Combined; Ethinyl Estradiol; Female; Histocytochemistry; Humans; Keratins; Liver; Liver Neoplasms; Microscopy, Electron; Norethindrone; Time Factors | 1987 |
Absence of cytokeratin in human hepatoma cell lines.
The immunofluorescence study revealed that both our established human hepatoma cell lines, HA22T/VGH and HA47T/VGH, were absent of cytokeratin. This observation was further confirmed by a western blot study. However, they as well as the other human hepatoma cells, Hep G2, Hep 3B, and SK-Hep-1 expressed vimentin. Topics: Carcinoma, Hepatocellular; Cell Line; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Humans; Immunoassay; Intermediate Filaments; Keratins; Liver Neoplasms; Vimentin | 1987 |
Hepatoblastoma: an immunohistochemical and ultrastructural study.
The ultrastructural and immunohistochemical features of 19 hepatoblastomas were examined to evaluate the phenotypic expressivity of this solid embryonic neoplasm of childhood. Electron microscopy confirmed the embryonal and fetal characteristics of the neoplastic hepatocytes, but in addition, cells with features intermediate between these two cell types were identified. Dense bundles of collagen corresponding to the osteoid-like material by light microscopy surrounded nests of cells; the cells within this matrix stained for epithelial membrane antigen and vimentin and focally for cytokeratin, and they showed ultrastructural features of epithelial cells. The two cases of small cell hepatoblastoma reacted positively for vimentin and cytokeratin; the remaining 17 cases were immunoreactive for cytokeratin and alpha-fetoprotein, and some also for alpha 1-antitrypsin, ferritin, and vimentin. A histogenetic scheme based on our findings is proposed to explain the divergent morphologic features of this neoplasm. Topics: alpha 1-Antitrypsin; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Infant; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Mucin-1; S100 Proteins; Vimentin | 1987 |
Comparison of mouse and human keratin 18: a component of intermediate filaments expressed prior to implantation.
Keratin 18 is a type-I keratin that is found in a variety of simple epithelial tissues. In mice, the corresponding protein, called Endo B, is expressed at the 4- to 8-cell stage of mouse development and may be one of the first intermediate-filament proteins synthesized after fertilization. A cDNA clone for keratin 18, designated pK18, was isolated from a human placental cDNA library by hybridization with the mouse Endo-B probe. It was characterized by hybridization selection of RNA, translation, immunoprecipitation, Northern blotting, and sequence analysis. Synthetic T7 polymerase transcripts of the cDNA were indistinguishable in size from keratin-18 mRNA, suggesting that pK18 represents a full-length copy of the RNA. The cDNA insert is 1,428 nucleotides long and contains a single open reading frame of 1,342 nucleotides coding for 429 amino acids. The deduced amino acid sequence is 89.7% identical with that of Endo B. The only extensive difference between the two sequences is due to 9 additional amino acids being present in the last half of the N-terminal domain of keratin 18. The 38-nucleotide-long 3' noncoding region of the cDNA is 75% identical with the corresponding portion of Endo B. The 5' noncoding regions are 59% identical. The expression of keratin-18 mRNA was found to vary more than tenfold when HeLa cells and BeWo trophoblastic cells were compared. Topics: Amino Acid Sequence; Animals; Base Sequence; Carcinoma, Hepatocellular; Cell Line; Cloning, Molecular; DNA; Embryonic Development; Female; Humans; Keratins; Liver Neoplasms; Mice; Nucleic Acid Hybridization; Placenta; Pregnancy; RNA, Messenger; Species Specificity | 1986 |
Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study.
Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. In a review of 24 cases of this tumor, three histologic types were encountered. Four cases were Type I or "collision tumors," apparently a coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma in the same patient. Twelve cases were Type II or "transitional tumors," in which there were areas of intermediate differentiation and an identifiable transition between hepatocellular carcinoma and cholangiocarcinoma. Eight cases were Type III or "fibrolamellar tumors" which resembled the fibrolamellar variant of hepatocellular carcinoma but which also contained mucin-producing pseudoglands. Type III tumors differ from other combined tumors, occurring at a younger age, in the absence of cirrhosis, and having a slightly longer survival. Immunohistochemical (immunoperoxidase) staining for intracellular antigens showed that alpha-fetoprotein is a fairly specific, although insensitive, marker of hepatocellular differentiation in primary liver cancers, being present in 50% of typical hepatocellular carcinomas and in hepatocellular areas in 29% of combined tumors, but in no cholangiocarcinomas or cholangiocellular areas of combined tumors. Keratin is a good marker of biliary epithelial differentiation, being found in 90% of cholangiocarcinomas and in 52% of combined hepatocellular cholangiocarcinomas, but in no hepatocellular carcinomas. Alpha-1-antitrypsin, fibrinogen, IgG, and carcinoembryonic antigen may be found in both hepatocellular carcinoma, cholangiocarcinoma, and in combined tumors; these antigens are therefore of limited use in differential diagnosis. Topics: Adenoma, Bile Duct; Adolescent; Adult; Aged; alpha-Fetoproteins; Carcinoma, Hepatocellular; Female; Fibrinogen; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis | 1985 |
Studies on the proliferation and fate of oval cells in the liver of rats treated with 2-acetylaminofluorene and partial hepatectomy.
The kinetics of oval cell proliferation in the liver and their fate were studied by combined autoradiography and immunohistochemical staining for epidermal prekeratin and epoxide hydrolase (EH). The oval cell proliferation was induced in rats by exposure to dietary 2-acetylaminofluorene (2-AAF) for 2 weeks with the midway performance of partial hepatectomy (PH). The labeling with 3H-thymidine [3H-TdR] was done in different groups of rats by two procedures: continuous exposure for 1 week with the aid of a minipump and brief exposure by the administration of a single dose. The livers of groups of animals were examined from 1 to 10 weeks after PH. Oval cells and duct epithelium showed positive staining for prekeratin and negative for EH, whereas hepatocytes showed the reverse pattern of staining. A critical finding was the observation that the exposure to the 2-AAF inhibited virtually completely the labeling of hepatocytes with [3H]-TdR in the caudate lobe and incompletely in the right lobe without interfering with the labeling of the oval cells in either lobe. This made it possible to study the fate of the oval cells vis-à-vis hepatocytes. This qualitative-quantitative study of oval cells and hepatocytes clearly indicates that oval cells under these experimental conditions do not become hepatocytes within 10 weeks. Over 80% of oval cells disappear within this period, and the remainder persist as such. These results indicate that under one set of experimental conditions related to hepatocarcino-genesis in the rat, no evidence for the conversion of oval cells to hepatocytes was obtained. Topics: 2-Acetylaminofluorene; Animals; Carcinoma, Hepatocellular; Cell Division; Disease Models, Animal; Epoxide Hydrolases; Hepatectomy; Histocytochemistry; Immunoenzyme Techniques; Keratins; Liver; Liver Neoplasms; Male; Organ Size; Protein Precursors; Rats; Rats, Inbred F344 | 1984 |
Cytokeratin filament expression during in vitro teratocarcinoma cell differentiation as detected by a monoclonal antibody.
Undifferentiated F9 teratocarcinoma cells were induced to differentiate in culture using retinoic acid and cAMP. As a result the morphology of the cultures changes dramatically. Using a monoclonal antibody directed against cytokeratin polypeptide 18 (RGF 53) in the indirect immunofluorescence technique we could show that this cytokeratin subunit is synthesized and assembled into a filamentous network upon differentiation in about 50% of the cells. Immunoblotting studies confirm these results. Topics: Animals; Antibodies, Monoclonal; Carcinoma, Hepatocellular; Cell Differentiation; Cell Line; Cytoskeleton; Humans; Keratins; Liver Neoplasms; Mice; Microscopy, Phase-Contrast; Teratoma | 1984 |
Cytokeratin filament expression during in vitro teratocarcinoma cell differentiation as detected by a monoclonal antibody.
Undifferentiated F9 teratocarcinoma cells were induced to differentiate in culture using retinoic acid and cAMP. As a result, the morphology of the cultures changes dramatically. Using a monoclonal antibody directed against cytokeratin polypeptide 18 (RGE 53) in the indirect immunofluorescence technique we could show that this cytokeratin subunit is synthesized and assembled into a filamentous network upon differentiation in about 50% of the cells. Immunoblotting studies confirm these results. Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; Carcinoma, Hepatocellular; Cell Differentiation; Cell Line; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Mice; Neoplasm Proteins; Teratoma | 1984 |
Protein complexes of intermediate-sized filaments: melting of cytokeratin complexes in urea reveals different polypeptide separation characteristics.
Subunit complexes of cytokeratin polypeptides from intermediate-sized filaments (IF) of various tissues and cultured cells from rat, cow, and man were solubilized in low-salt buffer containing 4 M urea and exposed to increasing concentrations of urea, followed by urea gradient electrophoresis or two-dimensional gel electrophoresis at different urea concentrations. Correspondingly, cytokeratin polypeptides dissociated in 9.5 or 10 M urea were dialyzed into lower concentrations of urea and allowed to reassociate into specific complexes. It was found that the polypeptide constituents of a given cytokeratin complex dissociate in the form of a rather sharp "melting curve" and that dissociated polypeptides reassociate in the same mode of dependence on urea concentration. The midpoint of melting in urea (Um) is a characteristic property of a given complex of cytokeratin polypeptides. Um values differ markedly between different cytokeratin complexes, ranging from 5.9 to 9.0 M urea. The results also show that cytokeratins do not form complexes with vimentin, another type of IF protein. The data suggest that certain cytokeratin polypeptides are complementary and contain sequences that direct their association into specific complexes forming IF subunits. Topics: Animals; Breast Neoplasms; Carcinoma, Hepatocellular; Cattle; Cell Line; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; HeLa Cells; Humans; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Liver Neoplasms, Experimental; Macromolecular Substances; Protein Denaturation; Rats; Solubility; Urea | 1983 |
Monoclonal antibodies to intermediate filament proteins of human cells: unique and cross-reacting antibodies.
Monoclonal antibodies were generated against the intermediate filament proteins of different human cells. The reactivity of these antibodies with the different classes of intermediate filament proteins was determined by indirect immunofluorescence on cultured cells, immunologic indentification on SDS polyacrylamide gels ("wester blot" experiments), and immunoperoxidase assays on intact tissues. The following four antibodies are described: (a) an antivimentin antibody generated against human fibroblast cytoskeleton; (b), (c) two antibodies that recognize a 54-kdalton protein in human hepatocellular carcinoma cells; and (d) an antikeratin antibody made to stratum corneum that recognizes proteins of molecular weight 66 kdaltons and 57 kdaltons. The antivimentin antibody reacts with vimentin (58 kdaltons), glial fibrillary acidic protein (GFAP), and keratins from stratum corneum, but does not recognize hepatoma intermediate filaments. In immunofluorescence assays, the antibody reacts with mesenchymal cells and cultured epithelial cells that express vimentin. This antibody decorates the media of blood vessels in tissue sections. One antihepatoma filament antibody reacts only with the 54 kdalton protein of these cells and, in immunofluorescence and immunoperoxidase assays, only recognizes epithelial cells. It reacts with almost all nonsquamous epithelium. The other antihepatoma filament antibody is much less selective, reacting with vimentin, GFAP, and keratin from stratum corneum. This antibody decorates intermediate filaments of both mesenchymal and epithelial cells. The antikeratin antibody recognizes 66-kdalton and 57-kdalton proteins in extracts of stratum corneum and also identifies proteins of similar molecular weights in all cells tested. However, by immunofluorescence, this antibody decorates only the intermediate filaments of epidermoid carcinoma cells. When assayed on tissue sections, the antibody reacts with squamous epithelium and some, but not all, nonsquamous epithelium. Therefore this antistratum corneum antibody and the anti-54-kdalton antibody identify unique epitopes present in the various cytokeratin molecules of epithelial cells. None of the hybridoma antibodies react with neurofilament proteins. The different patterns of reactivity of these antibodies suggest that many of the immunologically distinct intermediate filament proteins contain common antigenic determinants. Topics: Antibodies, Monoclonal; Carcinoma, Hepatocellular; Cell Line; Cross Reactions; Epidermis; Epitopes; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Humans; Hybridomas; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Peptides; Vimentin | 1982 |
Identification of Mallory bodies with rhodamine B fluorescence and other stains for keratin.
Rhodamine B staining in conjunction with fluorescence microscopy is shown to demonstrate Mallory bodies. Mallory body morphology, localization, and distribution in hepatocytes from griseofulvin-fed mice, human hepatoma, and human alcoholics were similar to those observed in the same tissues after conventional staining methods for Mallory bodies. The presence of these inclusions was further confirmed by specific cytochemical localization with indirect immunoperoxidase labeling, horseradish peroxidase labeling, and electron microscopy. Other tinctorial or histochemical procedures previously used for keratin or prekeratin (modified Mallory stain, Kreyberg method, Pauly method for histidine) also stained Mallory bodies for study with white light microscopy but with decreasing sensitivity respectively. Mallory bodies from mouse and human liver both appear to contain a keratin-like moiety. This entity may be simply, rapidly, and permanently stained with rhodamine B, and selectively and reproducibly demonstrated with fluorescence microscopy. Topics: Animals; Carcinoma, Hepatocellular; Endoplasmic Reticulum; Griseofulvin; Humans; Keratins; Liver; Liver Diseases, Alcoholic; Liver Neoplasms; Mice; Microscopy, Fluorescence; Rhodamines; Staining and Labeling; Xanthenes | 1981 |