PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.
Area Under Curve ; Biomarkers/blood/metabolism ; Biomarkers, Tumor/blood ; Carcinoma, Hepatocellular/blood/*diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*blood/*metabolism ; Liver Neoplasms/blood/*diagnosis ; Male ; Middle Aged ; Protein Precursors/blood/metabolism ; Prothrombin/metabolism ; ROC Curve ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; alpha-Fetoproteins/analysis/metabolism

BACKGROUND/AIMS: We tried to investigate the expression characteristics of KAI1, a suppressor of wide-spectrum tumor metastasis, and vascular endothelial growth factor (VEGF), the most common angiogenesis factor, and then to analyze their diagnostic value for hepatocellular carcinoma (HCC). METHODS: The protein and mRNA expression levels of KAI1 or VEGF in HCC tissues and in self-controlled para-carcinoma tissues were analyzed by Western blot and real-time polymerase chain reaction, respectively. Serum levels of KAI1 and VEGF in the patients with HCC, benign liver disease or in healthy controls were quantitatively detected by enzyme-linked immunosorbent assay. RESULTS: The expression level of KAI1 was downregulated, while the expression level of VEGF was upregulated in the tissues or serum of the patients with HCC. The expression level of serum KAI1 in HCC patients was correlated with TNM staging, intrahepatic metastasis, lymph node or peritoneal metastasis, and portal vein thrombus. In addition to the factors that were correlated with KAI1 expression, VEGF expression was also closely related to the alpha-fetoprotein level of the patients. The area under the receiver operating characteristic curve for the diagnosis of HCC was 0.907 for KAI1 and 0.779 for VEGF. The sensitivity of serum KAI1 levels in the diagnosis of HCC was 86.96%; the accuracy was 83.06%, while the sensitivity, the accuracy and the negative predictive value were improved to 91.86%, 84.68%, and 78.79% according to the combined detection of KAI1 and VEGF, respectively. CONCLUSIONS: A combined detection of KAI1 and VEGF may greatly improve the efficiency of diagnosis and form a reliable panel of diagnostic markers for HCC.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD82/blood/genetics/*metabolism ; Carcinoma, Hepatocellular/blood/*diagnosis/genetics ; Case-Control Studies ; Female ; Gene Expression Regulation ; Humans ; Liver Diseases/genetics ; Liver Neoplasms/blood/*diagnosis/genetics ; Male ; Middle Aged ; Vascular Endothelial Growth Factor A/blood/genetics/*metabolism ; alpha-Fetoproteins/analysis

Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC. A combination of imaging and immuno-histochemical analysis is usually needed to make the diagnosis.
CA-19-9 Antigen/metabolism ; Carcinoma, Hepatocellular/mortality/pathology/radiography ; Cholangiocarcinoma/mortality/pathology/radiography ; Humans ; Liver Neoplasms/mortality/pathology/*radiography ; Magnetic Resonance Imaging ; Phenotype ; Risk Factors ; Survival Analysis ; Tomography, X-Ray Computed ; alpha-Fetoproteins/analysis

No abstract available.
Carcinoma, Hepatocellular/*pathology/therapy ; Cell Differentiation ; Chondrocytes/pathology ; Embolization, Therapeutic ; Ethanol/administration & dosage ; Giant Cells/pathology ; Humans ; Immunohistochemistry ; Liver Neoplasms/*pathology/therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Osteoclasts/pathology ; Vimentin/metabolism ; alpha-Fetoproteins/analysis

OBJECTIVETo establish a new function method for the analysis of a-fetoprotein (AFP) and beta-hCG in testicular tumors.

METHODSWe reexamined the serum levels of AFP and beta-hCG after radical orchiectomy, and calculated the measured coordinate, with the abscissa representing the number of the half-lives of tumor markers, and the ordinate representing the measured value of tumor markers. Referring to the measured value of tumor markers before surgery as a, the number of half-lives as x, and their theoretical value over a period of x elimination half-lives as y (logarithm to the base 2 of y), we calculated the predicted coordinate according to the formula y = log2(a/2x) ==> x + y = log2a (function 1). Then we assessed tumor residue and metastasis by analyzing the relationship between the measured and predicted coordinates.

RESULTSThe pathological examination of case 1 revealed a germ cell tumor of a mixed histological pattern of syncytiotrophoblast and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.22, 6.21) and (10, 8.38), and the predicted coordinates (2.22, 6.34) and (10, 4.41) , indicating the elimination of the yolk sac tumor and metastasis of the syncytiotrophoblast tumor. Case 2 demonstrated the mixed pathological nature of teratocarcinoma and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.67, -1.03) and (12, -3.32), and the predicted coordinates (2.67, 1.41) and (12, -5.80). But the review times of AFP and beta-hCG were out of the effective range of half-lives, with the measured values below the normal, which suggested no tumor residue or metastasis. Case 3 was found to be embryonal carcinoma. The measured coordinate of AFP was (0.22, 9.25) , and the predicted coordinate (0.22, 9.55) , indicating the elimination of tumor.

CONCLUSIONThe change of the tumor markers predicted by the function method coincided with the natural course of disease in the three cases. The coincidence of the measured with the predicted coordinate after radical orchiectomy indicates no metastasis, while their disagreement suggests possible residue and metastasis of the tumor.

Adult ; Biomarkers, Tumor ; blood ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Humans ; Male ; Models, Statistical ; Orchiectomy ; Testicular Neoplasms ; metabolism ; pathology ; alpha-Fetoproteins ; analysis

Gastric hepatoid adenocarcinoma is a special type of gastric carcinoma, which produces AFP. We report a case of an metastatic gastric hepatoid adenocarcinoma mistaken for primary hepatocellular carcinoma (HCC). A 72 year-old woman was transferred to our hospital for treatment of the hepatic mass. She underwent subtotal gastrectomy for gastric cancer 2 years ago. A year ago, she was diagnosed with hepatic mass and treated with transhepatic chemoembolization under the suspicion of primary HCC in other hospital. The hepatic mass looked like primary HCC on CT, and serum AFP was elevated to 18,735 IU/mL. We did the transhepatic mass biopsy and compared it to the histology of the previous gastric cancer. The results of immunohistochemical staining between them was coincident, and so it was diagnosed as a hepatic metastasis of gastric hepatoid adenocarcinoma.
Adenocarcinoma/*diagnosis/pathology/surgery ; Aged ; Carcinoma, Hepatocellular/*diagnosis/therapy ; Embolization, Therapeutic ; Endoscopy, Gastrointestinal ; Homeodomain Proteins/metabolism ; Humans ; Keratin-20/metabolism ; Keratin-7/metabolism ; Liver Neoplasms/diagnosis/*secondary/therapy ; Male ; Stomach Neoplasms/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; alpha-Fetoproteins/analysis

Gastric hepatoid adenocarcinoma is a special type of gastric carcinoma, which produces AFP. We report a case of an metastatic gastric hepatoid adenocarcinoma mistaken for primary hepatocellular carcinoma (HCC). A 72 year-old woman was transferred to our hospital for treatment of the hepatic mass. She underwent subtotal gastrectomy for gastric cancer 2 years ago. A year ago, she was diagnosed with hepatic mass and treated with transhepatic chemoembolization under the suspicion of primary HCC in other hospital. The hepatic mass looked like primary HCC on CT, and serum AFP was elevated to 18,735 IU/mL. We did the transhepatic mass biopsy and compared it to the histology of the previous gastric cancer. The results of immunohistochemical staining between them was coincident, and so it was diagnosed as a hepatic metastasis of gastric hepatoid adenocarcinoma.
Adenocarcinoma/*diagnosis/pathology/surgery ; Aged ; Carcinoma, Hepatocellular/*diagnosis/therapy ; Embolization, Therapeutic ; Endoscopy, Gastrointestinal ; Homeodomain Proteins/metabolism ; Humans ; Keratin-20/metabolism ; Keratin-7/metabolism ; Liver Neoplasms/diagnosis/*secondary/therapy ; Male ; Stomach Neoplasms/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; alpha-Fetoproteins/analysis

Combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC) is a rare subtype of primary liver cancer. We investigated the histopathologic features of transitional or intermediate areas in 21 combined HCC-CCs and immunophenotypes using different hepatic progenitor cell markers (CK7, CK19, c-kit, NCAM, and EpCAM). Major histologic findings of transitional or intermediate areas of 21 combined HCC-CCs included strands/trabeculae of small, uniform, oval-shaped cells with scant cytoplasm and hyperchromatic nuclei embedded within an abundant stroma, small cells with an antler-like anastomosing pattern, and solid nests of intermediate hepatocyte-like cells surrounded by small cells in periphery, in order of frequency. The intermediate area of one tumor was composed predominantly of spindle cells arranged in short fascicles. Immunophenotype of tumor cells with intermediate morphology suggested a progenitor cell origin for this tumor. Clinical findings of combined HCC-CC showed a closer resemblance with those of HCC than those of CC. In univariate analysis, tumor size, TNM stage, and serum alpha-fetoprotein levels showed a significant association with poor patient survival. Serum alpha-fetoprotein level was an independent prognostic indicator in multivariate analysis. In conclusion, an awareness of the clinicopathologic features, specifically the various morphologic features of intermediate areas in this tumor, is essential for prevention of potential misdiagnosis as another tumor.
Adult ; Aged ; Antigens, Neoplasm/metabolism ; Carcinoma, Hepatocellular/*pathology ; Cell Adhesion Molecules/metabolism ; Cholangiocarcinoma/*pathology ; Female ; Humans ; Immunophenotyping ; Keratin-19/metabolism ; Keratin-7/metabolism ; Liver Neoplasms/*pathology ; Male ; Middle Aged ; Neural Cell Adhesion Molecules/metabolism ; Prognosis ; Proto-Oncogene Proteins c-kit/metabolism ; alpha-Fetoproteins/analysis

No abstract available.
Female ; Hemangioendothelioma/metabolism/*pathology/surgery ; Humans ; Infant ; Interferon-alpha/therapeutic use ; Liver Neoplasms/metabolism/*pathology/surgery ; Tomography, X-Ray Computed ; alpha-Fetoproteins/*analysis

OBJECTIVETo study the applicability of MultiCalc software to prenatal screening of Down's syndrome in Jiangsu province, China.

METHODSThe gestational age-specific median of maternal serum marker was calculated by means of regression method. Regression functions for adjustment of Multiple of the Median (MoM) by weight were established for our own population.

RESULTSBefore the adjustment by weight, the average level of alpha fetal protein(AFP) was 16% higher and the free beta-human chorionic gonadotrophin (beta-hCG) was 14% higher than those of the Caucasian in MultiCalc software respectively. But when the AFP and free beta-hCG results were converted to weight-adjusted MoM levels, the values were 0.99 and 1.02 respectively. The median of MoM of AFP and the free beta-hCG were 1.00 through the regression model of gestational age and weight adjustment.

CONCLUSIONThere was no difference of average weight-adjusted MoM levels between the Jiangsu population and the Caucasian, and the MultiCalc software was applicable to maternal serum screening for Down's syndrome of Jiangsu.

Adolescent ; Adult ; Body Weight ; China ; Chorionic Gonadotropin ; blood ; Down Syndrome ; diagnosis ; Female ; Fetal Diseases ; diagnosis ; Gestational Age ; Humans ; Middle Aged ; Mothers ; Pregnancy ; Pregnancy Trimester, Second ; blood ; Prenatal Diagnosis ; methods ; Reference Values ; Regression Analysis ; Software ; alpha-Fetoproteins ; metabolism