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

To better understand the mechanism underlying hepatocellular carcinoma (HCC) metastasis and to search for potential markers for HCC prognosis, differential proteome analysis on two HCC cell strains with high and low metastatic potentials, MHCC97-H and MHCC97-L, was conducted using two-dimensional (2-D) gel electrophoresis followed by matrix-assisted laser desorption/time of flight mass spectrometry and liquid chromatography ion trap mass spectrometry. Image analysis of silver-stained 2-D gels revealed that 56 protein spots showed significant differential expression in MHCC97-H and MHCC97-L cells (Student's t-test, P < 0.05) and 4 protein spots were only detected in MHCC97-H cells. Fourteen protein spots were further identified using in-gel tryptic digestion, peptide mass fingerprinting and tandem mass spectrometry. The expressions of pyruvate kinase M2, ubiquitin carboxy-terminal hydrolase L1, laminin receptor 67 kDa, S100 calcium-binding protein A4, thioredoxin and cytokeratin 19 were elevated in MHCC97-H cells. However, manganese superoxide dismutase, calreticulin precursor, cathepsin D, lactate dehydrogenase B, non-metastatic cell protein 1, cofilin 1 and calumenin precursor were down-regulated in MHCC97-H cells. Intriguingly, most of these identified proteins have been reported to be associated with tumor metastasis. The functional implications of alterations in the levels of these proteins are discussed.
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PMID:Proteome analysis of hepatocellular carcinoma cell strains, MHCC97-H and MHCC97-L, with different metastasis potentials. 1504 80

Cholangiocarcinoma (CCA), a malignant tumor derived from bile duct epithelium, occurs with a higher incidence in tropical countries, such as Thailand. Distinguishing CCA from hepatocellular carcinoma (HCC) of the liver often requires the use of histochemistry, so molecular markers for diagnosis and prognosis are still required. In this study, the two-dimensional (2-D) protein map of a Thai human bile duct epithelial carcinoma cell line (HuCCA-1) has been compared to human hepatocellular carcinoma cell lines (HepG2 and HCC-S102) and a human breast epithelial cancer cell line (MCF-7). Our results show that HuCCA-1 expressed a unique pattern of proteins. Forty-three major proteins were identified by matching to the map of MCF-7, and by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray ionization-tandem MS (ESI-MS/MS). Cytokeratins CK8 and CK18 were overexpressed in both HuCCA-1 and HCC, while CK7 and CK19 were only expressed in HuCCA-1. Four specific proteins with MW/pI 57.2/5.21 (U1, vimentin), 42.2/6.20 (U2), 43.2/6.20 (U3, EF-TU), and 42.2/6.40 (U4, unidentified) were absent from HepG2. U2 showed high expression in HuCCA-1, while U1 and U4 showed high expression in HCC-S102. U2 could be separated in 2 proteins, U2/1 (alpha-enolase) and U2/2 (not identified) by using IPG pH 4-7. Galectin-3 showed high expression level in HuCCA-1 by 1-DE immunodetection, and gave only one spot with MW 32.9 kDa and pI 8.29 on 2-DE immunoblotting, Thus, certain proteins, namely CK7, CK19, U2/2 and galectin-3, may be good markers useful for differential diagnosis of cholangiocarcinoma compared to hepatocellular carcinoma.
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PMID:Proteomic analysis of cholangiocarcinoma cell line. 1504 94

A 5-cm lesion in the right hepatic lobe was detected in a 61-year-old man with chronic hepatitis C by ultrasonography. Contrast-enhanced computed tomography showed a low-density lesion with wide peripheral enhancement. Hepatic angiography revealed that the tumor had partial hypervascularity. Although serum concentrations of alpha-fetoprotein and carcinoembryonic antigen were within normal limits, an elevated concentration of carcinohydrate antigen 19-9 was detected in serum. A definitive diagnosis was not made although we strongly suspected mixed hepatocellular carcinoma and cholangiocarcinoma. Since intraoperative frozen-section examination revealed adenocarcinoma, a right hepatic lobectomy with regional lymph node dissection was performed. A histologic diagnosis of mixed hepatocellular carcinoma and cholangiocarcinoma was made because the hepatic tumor consisted of components of both hepatocellular carcinoma and cholangiocellular carcinoma, with a transitional area. Additionally, immunohistochemical examination revealed that some tumor cells in the transitional area were immunoreactive for both cytokeratin 19 and hepatocyte paraffin 1.
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PMID:A mixed hepatocellular carcinoma and cholangiocarcinoma: dual expression of biliary-type cytokeratin and hepatocyte specific marker. 1514 30

Molecular markers (biomarkers) for hepatocellular carcinoma (HCC) metastasis and recurrence could provide additional information to that gained from traditional histopathological features. A large number of biomarkers have been shown to have potential predictive significance. One important aspect of this is to detect the transcripts of tumor-associated antigens (such as AFP, MAGEs, and CK19), which are proposed as predictive markers of HCC cells disseminated into the circulation and for metastatic recurrence. Another important aspect is to analyze the molecular markers for cellular malignancy phenotype, including DNA ploidy, cellular proliferation index, cell cycle regulators, oncogenes, and tumor suppressors (especially p53 gene), as well as telomerase activity. Molecular factors involved in the process of HCC invasion and metastasis, including adhesion molecules (E-cadherin, catenins, ICAM-1, laminin-5, CD44 variants, osteopontin), proteinases responsible for the degradation of extracellular matrix (MMPs, uPA system), as well as angiogenesis regulators (such as VEGF, intratumor MVD), have also been shown to be potential predictors for HCC metastatic recurrence and clinical outcomes. One important new trend is to widely delineate biomarkers with genomic and proteomic expression with reference to predicting metastatic recurrence, molecular diagnosis, and classification, which has been drawing more attention recently. Body fluid (particularly blood and urine) testing for biomarkers is easily accessible and more useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum and its genetic alterations is another important direction. More attention should be paid to these areas in the future. As understanding of tumor biology deepens, more and more new biomarkers with high sensitivity and specificity for HCC metastatic recurrence could be found and routinely used in clinical assays. However, the combination of the pathological features and some of the biomarkers mentioned above seems to be more practical up to now.
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PMID:Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature. 1520 47

We experienced a resected case of a small hepatocellular carcinoma, which required differential diagnosis from intrahepatic cholangiocellular carcinoma. The patient was a 76-year-old man. While his course had been being observed because of hepatitis C antibody-positive liver cirrhosis, ultrasonographic examination of the abdomen revealed dilation of biliary branches in the anterior segment of the liver and a hyperechoic mass 10 mm in diameter at the origin of the branch. A dynamic computed tomography scan showed a high-density tumor in the early phase. After embolization of the right branch of the portal vein, resection of the right lobe of the liver and the extrahepatic bile duct was performed. A resected specimen showed a white-colored mass 8 mm in diameter at the origin of the anterior segmental biliary branch. In the pathological findings, the diagnosis was a poorly differentiated hepatocellular carcinoma with strong nuclear atypia; the tumor filled the bile duct, forming a trabecular structure. The immunohistological stains of the tumor were positive for cytokeratin (CK) 8, CK18, and HepParl and negative for alpha-fetoprotein, carcinoembryonic antigen, CA19-9, CK7, CK19, and CK20. There was atypia in the biliary lining epithelium adjacent to the tumor, and the hepatocellular carcinoma may have developed from the biliary epithelium.
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PMID:A resected case of a small hepatocellular carcinoma developing within the bile duct. 1523 93

There are many molecular tumor markers for diagnosing and monitoring cancer patients. Especially, quantitative assay for serum levels of tumor markers; such as AFP, CEA, PSA, hCG, CA 19-9 and CA 125, are frequently used in daily practice because of their relative specificities and usefulness to the common cancers. Though not suitable for early diagnosis, but they are used in monitoring patients with advanced caner, especially after treatments. Two of them, AFP and PSA, are also used in the screening and monitoring of high-risk groups, namely patients with chronic viral hepatitis and old male, who are the high risk for hepatoma and proste cancer respectively. Problems in using serum markers are; relatively low specificity and low sensitivity to cancer, confusing naming for similar markers that recognize almost the same molecule of cancer. Users must understand that CA 19-9, CA 50, KM-O 1 and SPAN-1 are in the same sialylated Lewis A group, and CA 125, CA 130 and CA 602; in the mucin antigen group, and STN, CA 54/61 and CA 72-4; in the sialyl Tn antigen group. Combination of two or more markers may inform us the biological characteristics of the cancer. For example, a germ-cell tumors may produce hCG and placental marker. That is of the choriocarcinoma type. Those with hCG and fetal antigens are the ordinal type of germ cell tumors, and those with AFP, CEA and cytokeratin are teratoma, and those with LDH and ALP only but negative for hCG and AFP must be seminoma. For the bronchial and alveolar carcinomas, CEA, SCC, NSE and cytokeratin 19 fragments are useful. Combination may be difficult for beginners but once understood, it will be an art in clinical oncology.
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PMID:[Clinical usefulness of circulating tumor markers]. 1527

Hepatocellular carcinoma (HCC) has distinct morphologic features and can be identified in the majority of cases by routine hematoxylin and eosin (H&E)-stained formalin-fixed paraffin-embedded sections. However, distinguishing a well-differentiated HCC from normal or regenerative tissue may be very difficult in some cases, particularly in small needle aspiration or core biopsies. Furthermore, some of the unusual morphologic variants, including clear-cell, pleomorphic, and sarcomatoid variants, may be mistaken for metastases. Similarly, metastases from various primary tumors to the liver may be mistaken for primary hepatic tumors. In this overview, we summarize the immunohistochemical and molecular markers that have been developed to address these diagnostic challenges. Among the numerous diagnostic markers studied, pCEA, HepPar 1, CD34, CK 7, CK 19, CK 20, and albumin in situ (ISH) have been found to be valuable in distinguishing HCC from metastatic neoplasms of extrahepatic sites.
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PMID:Immunohistochemical and molecular markers in the diagnosis of hepatocellular carcinoma. 1532 90

Hepatocellular carcinoma is generally refractory to clinical treatment. Here, we report that inactivation of the MYC oncogene is sufficient to induce sustained regression of invasive liver cancers. MYC inactivation resulted en masse in tumour cells differentiating into hepatocytes and biliary cells forming bile duct structures, and this was associated with rapid loss of expression of the tumour marker alpha-fetoprotein, the increase in expression of liver cell markers cytokeratin 8 and carcinoembryonic antigen, and in some cells the liver stem cell marker cytokeratin 19. Using in vivo bioluminescence imaging we found that many of these tumour cells remained dormant as long as MYC remain inactivated; however, MYC reactivation immediately restored their neoplastic features. Using array comparative genomic hybridization we confirmed that these dormant liver cells and the restored tumour retained the identical molecular signature and hence were clonally derived from the tumour cells. Our results show how oncogene inactivation may reverse tumorigenesis in the most clinically difficult cancers. Oncogene inactivation uncovers the pluripotent capacity of tumours to differentiate into normal cellular lineages and tissue structures, while retaining their latent potential to become cancerous, and hence existing in a state of tumour dormancy.
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PMID:MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. 1547 48

Alpha-fetoprotein producing tumors other than hepatoma and germ cell tumors have been widely reported, especially in carcinoma with hepatoid differentiation (hepatoid carcinoma). Hepatoid carcinoma has mostly been found in the stomach, but also occurs in many other organs. A rare case of hepatoid carcinoma of the ovary is presented. A 57-year-old Taiwanese woman was admitted because of lower abdominal pain. Magnetic resonance imaging showed a 10 cm right adnexal mass. She underwent a total hysterectomy and bilateral salpingo-oophorectomy with omentectomy. A right ovarian mass measuring 13 x 9 x 8 cm was found. Microscopic examination showed characteristic features for hepatoid carcinoma. Immunohistochemical staining was performed on the tumor using a panel of eight markers (AFP, p-CEA, CD10, Hep Par 1, thyroid transcription factor-1, CK7, CK19 and CK20). This study contradicts the theory that hepatoid carcinoma derives from the surface epithelium of the ovary. Hepatoid carcinoma of the ovary commonly contains a population of clear cells, which may lead to the misdiagnosis of yolk sac tumor or clear cell adenocarcinoma that may arise in many anatomic sites. Histologically, it is also difficult to distinguish hepatoid carcinoma from hepatoid yolk sac tumor. In such cases, demonstration of CD 10, Hep Par 1, membraneous patterns of p-CEA and CK7 would be invaluable for characterizing the tumor as hepatoid carcinoma. More studies are needed to confirm this observation.
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PMID:Hepatoid carcinoma of the ovary: characteristics of its immunoreactivity. A case report. 1559 58

A case of primary hepatic carcinoma is reported, which occurred in a 24-year-old woman with a 10-year history of oral contraceptive use, and demonstrated unique morphologic and immunohistochemical features. The tumor was located in the left hepatic lobe, measured 14 cm at its widest, and showed histologic heterogeneity. The neoplastic cells were mostly arranged in trabecular and pseudoglandular growth patterns simulating hepatocellular carcinoma; however, in focal areas, small cystic, organoid and tubular patterns predominated. Immunohistochemical stains showed a phenotype consistent with biliary differentiation (positive staining for cytokeratin 7, cytokeratin 19, carcinoembryonic antigen and CA 19-9 antigen). The tumor cells were negative for markers that would be suggestive of hepatocytic or neuroendocrine differentiation. Interestingly, they were positive for inhibin, a protein that is known to be expressed in sex cord-stromal tumors of the ovary, trophoblastic neoplasms and adrenal cortical tumors, but not in hepatic tumors. However, no definite evidence of gonadal stromal, trophoblastic, or adrenocortical differentiation was identified on extensive immunohistochemical work-up. In conclusion, this unique case may represent a rare variant of cholangiocarcinoma expressing inhibin.
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PMID:Hepatic adenocarcinoma expressing inhibin in a young patient on oral contraceptives. 1581 32


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