Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.
Adenoma, Liver Cell ; Bone Marrow ; Carcinoma, Hepatocellular ; Female ; Humans ; Liver ; Metaplasia ; Ultrasonography ; Young Adult

No abstract available.
Adenoma, Liver Cell* ; Carcinoma, Hepatocellular*

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality in part due to its high resistance to chemotherapeutic drugs. The anti-apoptotic Mcl-1 expression has been reported as a resistance factor in various types of tumors. Here, we investigated the expression of Mcl-1 in hepatoma cells and HCC tissues and its relationship with p53, and analyzed the possibility of the gene as a molecular target for HCC therapy. HCC specimens of 30 patients were examined by immunohistochemistry for Mcl-1 and p53 expression. Mcl-1 expression in hepatoma cell lines was measured by RT-PCR and Western blotting. The suppression of Mcl-1 by RNA interference or specific phosphatidylinositol-3 kinase (PI3K) inhibitor, LY294002, was evaluated as monotherapy, and it was combined with mitomycin C (MMC) in treating hepatoma cell line HepG2. Cell viability and apoptosis were assessed by MTT and FACS analysis. Finally, changes of Mcl-1 or p53 expression in various hepatoma cell lines were examined after transfection with Mcl-1 siRNA, the Mcl-1 expression plasmid, or the wide-type p53 expression plasmid, respectively. Mcl-1 protein was remarkably enhanced in HCC tissues as compared with adjacent non-tumor liver tissues. In addition, Mcl-1 was prominently expressed in HepG2 and Hep3B cells, weakly in SMMC7721 cells, and not in L02 cells. P53 protein was also overexpressed in HCC tissues and there was a significant correlation between the expression of p53 and Mcl-1. Silencing Mcl-1 by RNAi or LY294002 downregulated Mcl-1 expression and led to decreased cell viability and increased apoptosis. Combination of MMC and Mcl-1 RNAi or LY294002 exhibited a significant chemosensitizing effect. The expression of p53 was not influenced by Mcl-1 siRNA in HepG2 cells or transfection with the Mcl-1 expression plasmid in L02 cells. Furthermore, the expression of Mcl-1 in Hep3B cells was also not significantly changed after transfection with the wild-type p53 expression plasmid. It is concluded that Mcl-1 is overexpressed in HCC tissues. The mechanisms by which silencing Mcl-1 sensitizes hepatoma cells towards chemotherapy may be not attributed to the upregulated expression of p53 but the dysfunction of p53 through Mcl-1/p53 interaction. Mcl-1 may be a potential target of gene therapy for HCC.
Adenoma, Liver Cell ; drug therapy ; genetics ; pathology ; Apoptosis ; drug effects ; Biomarkers, Tumor ; biosynthesis ; genetics ; Chromones ; administration & dosage ; Gene Expression Regulation, Neoplastic ; drug effects ; Hep G2 Cells ; Humans ; Liver Neoplasms ; drug therapy ; genetics ; pathology ; Morpholines ; administration & dosage ; Myeloid Cell Leukemia Sequence 1 Protein ; biosynthesis ; genetics ; RNA, Small Interfering ; genetics ; Transfection ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

Clonorchis sinensis is a Group-I bio-carcinogen, associated with cholangiocarcinoma (CCA). The hamster is the only experimental model of C. sinensis-mediated CCA, but we oblige another animal model. The present study intended to develop a C. sinensis (Cs) mediated CCA model using C3H/He mice, co-stimulated with N-nitrosodimethyl-amine (NDMA) and dicyclanil (DC). The mice were divided into 8 groups with different combinations of Cs, NDMA, and DC. Six months later the mice were sacrificed and subjected to gross and histopathological examination. The body weights were significantly reduced among the groups treated with 2 or more agents (eg. Cs+NDMA, Cs+DC, NDMA+DC, and Cs+NDMA+DC). In contrast, liver weight percentages to body weight were increased in above groups by 4.1% to 4.7%. A Change of the spleen weight was observed only in Cs+NDMA group. Though C. sinensis infection is evident from hyperplastic changes, only 1 worm was recovered. T wo mice, 1 from Cs and the other from Cs+DC group, showed mass forming lesions; 1 (281.2 mm3) from the Cs group was a hepatocellular adenoma and the other (280.6 mm3) from the Cs+DC group was a cystic mass (peliosis). Higher prevalence of gray-white nodules was observed in Cs group (42.9%) followed by Cs+NDMA+DC group (21.4%). The mice of the Cs+NDMA+DC group showed hyper-proliferation of the bile duct with fibrotic changes. No characteristic change for CCA was recognized in any of the groups. In conclusion, C3H/He mice produce no CCA but extensive fibrosis when they are challenged by Cs, NDMA, and DC together.
Adenoma, Liver Cell ; Animals ; Bile Ducts ; Body Weight ; Cholangiocarcinoma* ; Clonorchis sinensis* ; Cricetinae ; Dimethylnitrosamine* ; Fibrosis ; Liver ; Mice* ; Models, Animal ; Models, Theoretical ; Prevalence ; Spleen

BACKGROUND: C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. METHODS: CRP immunoreactivity was examined in treatment-naive HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6). RESULTS: CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment. CONCLUSIONS: We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC.
Adenoma, Liver Cell ; C-Reactive Protein* ; Carcinoma, Hepatocellular* ; Cell Line ; Humans ; Immunoblotting ; Immunohistochemistry ; Interleukin-6 ; Liver ; Prognosis ; Real-Time Polymerase Chain Reaction ; RNA, Messenger

INTRODUCTIONHepatocellular adenomas (HCAs), with a risk of malignant transformation into hepatocellular carcinoma (HCC), classically develop in young women who are taking oral contraceptives. It is now clear that HCAs may also occur in men. However, it is rarely reported that HCAs with malignant transformation occur in male patients with non-cirrhotic livers. This study aimed to characterize the malignancy of HCAs occurring in male patients.

METHODSAll patients with HCAs with malignant transformation who underwent hepatectomy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 1999 and December 31, 2011 were enrolled in the study. The clinical characteristics as well as radiologic and pathologic data were reviewed.

RESULTSHCAs with malignant transformation were observed in 5 male patients with non-cirrhotic livers, but not in female patients. The alpha-fetoprotein (AFP) levels were higher in patients with HCAs with malignant transformation than in patients with HCAs without malignant transformation. The diameters of the tumors with malignant transformation were larger than 5 cm in 3 cases and smaller than 5 cm in 2 cases. The 5 patients were all alive without recurrence by the end of the study period. The disease-free survival times of the 5 patients were 26, 48, 69, 69, and 92 months.

CONCLUSIONOur results indicate that resection would be advised even if the presumptive diagnosis is adenoma smaller than 5 cm in diameter, especially in male patients.

Adenoma, Liver Cell ; Beijing ; Carcinoma, Hepatocellular ; Cell Transformation, Neoplastic ; Contraceptives, Oral ; Disease-Free Survival ; Female ; Hepatectomy ; Humans ; Liver Cirrhosis ; Liver Neoplasms ; Male ; Neoplasm Recurrence, Local ; alpha-Fetoproteins

No abstract available.
Adenoma, Liver Cell/*diagnosis/diagnostic imaging/pathology ; Aged ; Antigens, CD34/metabolism ; Bile Ducts, Intrahepatic/pathology ; C-Reactive Protein/metabolism ; Female ; Humans ; Liver Neoplasms/*diagnosis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Serum Amyloid A Protein/metabolism ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Loss of liver fatty acid binding protein (LFABP) expression by immunohis-tochemistry is a useful marker for the identification of hepatocyte nuclear factor 1alpha (HNF1alpha)-inactivated hepatocellular adenomas; however, the expression status of LFABP in hepatocel-lular carcinomas (HCCs) is still unclear. We aimed to investigate the expression status of LFABP in HCCs and examine the clinicopathological characteristics of LFABP-negative HCCs. METHODS: Immunohistochemical stains LFABP, K19 (mouse monoclonal, Dako, Glostrup, Den-mark) and EpCAM (mouse monoclonal, Calbiochem, Darmstadt, Germany) were performed on tissue microarray sections from 188 surgically resected HCCs, and the association between LFABP expression status and the clinicopathological features, survival and "stemness"-related marker expression status were analyzed. RESULTS: Loss of LFABP expression was noted in 30 (16%) out of 188 HCCs. LFABP-negative HCCs were associated with a decreased recurrence-free survival (LFABP-negative: 17.0 +/- 4.84 months [95% confidence interval [CI]: 7.5-26.5 months] versus LFABP-positive: 51.0 +/- 8.7 months [95% CI: 34.0-68.0 months]; P=0.004). HCCs with LFABP expression loss were more frequently larger and showed more frequent vascular invasion, although not statistically sig-nificant; and an inverse correlation was seen between LFABP expression and K19 expression status (P=0.001). CONCLUSIONS: Loss of LFABP expression is seen in HCCs, and is associated with a decreased recurrence-free survival.
Adenoma, Liver Cell ; Carcinoma, Hepatocellular* ; Coloring Agents ; Fatty Acid-Binding Proteins* ; Hepatocyte Nuclear Factor 1-alpha ; Liver* ; Prognosis

Hepatocellular adenomas are a benign, focal, hepatic neoplasm that have been divided into four subtypes according to the genetic and pathological features. The beta-catenin activated subtype accounts for 10-15% of all hepatocellular adenomas and specific magnetic resonance imaging features have been defined for different hepatocellular adenomas subtypes. The current study aimed to report the magnetic resonance imaging features of a well differentiated hepatocellular carcinoma that developed on the basis of beta-catenin activated hepatocellular adenomas in a child. In this case, atypical diffuse steatosis was determined in the lesion. In the literature, diffuse steatosis, which is defined as a feature of the hepatocyte nuclear factor-1alpha-inactivated hepatocellular adenomas subtype, has not been previously reported in any beta-catenin activated hepatocellular adenomas case. Interlacing magnetic resonance imaging findings between subtypes show that there are still many mysteries about this topic and larger studies are warranted.
Adenoma ; Adenoma, Liver Cell ; beta Catenin* ; Carcinoma, Hepatocellular ; Child* ; Hepatocytes ; Humans ; Liver ; Liver Neoplasms ; Magnetic Resonance Imaging

Adenoma, Liver Cell ; Gallbladder Diseases ; Histiocytosis, Sinus ; Humans ; Liver Neoplasms