Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.
Humans ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/pathology* ; Prognosis ; Carnosine ; alpha-Fetoproteins/metabolism* ; Biomarkers, Tumor/genetics* ; Liver Cirrhosis/diagnosis* ; ROC Curve

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Adenoma/*diagnosis/surgery ; Carcinoma, Hepatocellular/diagnosis ; Diagnosis, Differential ; Focal Nodular Hyperplasia/*diagnosis/surgery ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/surgery ; beta Catenin/genetics/metabolism

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Adenoma/*diagnosis/surgery ; Carcinoma, Hepatocellular/diagnosis ; Diagnosis, Differential ; Focal Nodular Hyperplasia/*diagnosis/surgery ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/surgery ; beta Catenin/genetics/metabolism

OBJECTIVETo investigate the expression of IFITM3 in colorectal carcinoma and its clinical significance.

METHODS213 patients with colon ademocarcinoma and 214 patients with colon adenoma treated by surgery in our hospital from March 2008 to June 2010 were included in this study. The levels of IFITM3 in normal colon nucosa, adenoma, and adenocarcinoma tissues were detected by real-time PCR and immunochemistry, and its relationship with metastasis and prognosis in 213 colorectal cancer patients was analyzed.

RESULTSThe IFITM3 mRNA level in metastatic tumor group was 18.37 ± 0.61, significantly higher than that in the normal 4.49 ± 0.69 and non-metastases groups (7.32 ± 0.76; F = 460.380, P < 0.001). The positive rate of IFITM3 protein expression in metastatic tumor group (69.0%) was significantly higher than that in the normal (3.9%), non-metastasies groups (19.0%) and adenoma groups (11.3%). Our clinical analysis confirmed that the IFITM3 expression was associated with peritumoral invasion, hepatic metastases, metastases of para-colonic lymph nodes, mesocolonic lymph nodes and mesenteric root lymph nodes, omental metastasis and AJCC classification (P < 0.05). Furthermore, the survival curve analysis showed that patients with lower IFITM3 level expression had a higher 5-year survival rate (88.8%) than that in the patients with higher expression (40.2%, P < 0.001).

CONCLUSIONSIFITM3 expression has a positive correlation with metastasis and prognosis in patients with colorectal carcinoma.

Adenocarcinoma ; diagnosis ; metabolism ; Adenoma ; Colorectal Neoplasms ; diagnosis ; metabolism ; Humans ; Liver Neoplasms ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Neoplasms ; Peritoneal Neoplasms ; Prognosis ; RNA, Messenger ; RNA-Binding Proteins ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; Survival Analysis ; Survival Rate

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

OBJECTIVETo study the clinicopathologic features, immunophenotype, histological diagnosis and prognosis of hepatic epithelioid angiomyolipoma.

METHODSClinical data of 25 cases of hepatic epithelioid angiomyolipoma were collected along with follow-up study of the patients. The pathological features were documented and immunohistochemical study of various markers was performed with an emphasis on diagnosis and differential diagnosis.

RESULTSHepatic epithelioid angiomyolipoma was more commonly found in young women without characteristic clinical symptoms. Its morphological features were characterized by marked cytological atypia, relatively rare mitotic figures; radial distribution of tumor cells around the thin-walled blood vessels or muscular vessels; and the presence of common multinucleated giant cells and large ganglion-like tumor cells. The tumor cells expressed both melanoma cell markers (HMB45, MART-1) and smooth muscle cell markers (SMA). Tumor cells expressed various other markers including ER 16% (4/25), PR 32% (8/25), TFE3 24% (6/25) and p53 60% (15/25).

CONCLUSIONSHepatic epithelioid angiomyolipoma has variable morphological features and characteristic immunohistochemical phenotype. The differential diagnoses include a variety of tumors. The biological behavior of the tumor tends to be benign.

Age Factors ; Angiomyolipoma ; genetics ; immunology ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms ; Giant Cells ; pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; Liver Neoplasms ; genetics ; immunology ; metabolism ; pathology ; MART-1 Antigen ; metabolism ; Melanoma-Specific Antigens ; metabolism ; Muscle, Smooth ; metabolism ; Prognosis

OBJECTIVETo study the expressions of β-catenin in hepatocellular carcinoma (HCC) tissue, adjacent cirrhotic liver tissue and hemangioma-surrounding liver tissue to understand whether their difference in expression will influence on the prognosis and to study the relationship between Wnt/β-catenin signaling pathway and HNF-1α expression.

METHODS50 specimens of HCC, 50 specimens of adjacent cirrhotic liver tissue and 7 specimens of hemangioma-surrounding liver tissue were used to detect the differences in the expression of β-catenin and HNF-1α in them by immunohistochemistry.

RESULTSThe expression rate of β-catenin was 74.0% (37/50) in the HCC tissue, 18.0% (9/50) in cirrhotic liver tissue, and 14.3% (1/7) in hemangioma-surrounding liver tissue. The expression rate of β-catenin in HCC tissue was significantly higher than that in the hemangioma-surrounding liver tissue (P = 0.002) and cirrhotic liver tissue (P < 0.001). The patients with abnormal expression had worse prognosis. Among the 50 HCC cases, the expression of HNF-1α was negative in 20.0% (10/50), weak positive in 40.0% (20/50), moderately positive in 26.0% (13/50), and strong positive in 14.0% (7/50). Among the 50 adjacent cirrhotic liver tissues, the expression of HNF-1α was negative in 12.0% (6/50), weak positive in 20.0% (10/50), moderately positive in 52.0% (26/50) and strong positive in 16.0% (8/50). In the 7 cases of hemangioma-surrounding liver tissue, the expression of HNF-1α was negative in 0(0/7), weak positive in 14.3% (1/7), moderately positive in 28.6% (2/7) and strong positive in 57.1% (4/7). The positive expression rate of HNF-1α in the HCC tissue was significantly lower than that in the hemangioma-surrounding liver tissues (P = 0.029) and adjacent cirrhotic liver tissues (P = 0.008). The patients with positive HNF-1α expression had a better prognosis. The abnormal expression of β-catenin was negatively correlated with positive HNF-1α expression (r = -0.673, P < 0.001).

CONCLUSIONSThe occurrence and development of HCC is related to the abnormal β-catenin expression. There is a negative correlation between Wnt/β-catenin signaling pathway and HNF-1α expression.

Carcinoma, Hepatocellular ; diagnosis ; metabolism ; Hemangioma ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Liver Neoplasms ; diagnosis ; metabolism ; Prognosis ; beta Catenin ; genetics ; metabolism

Human carboxylesterase 1 (HCE1), belonging to a multigene serine hydrolase family, is a major liver carboxylesterase responsible for the hydrolysis and metabolism of various xenobiotics. It also plays an important role in the transportation and metabolism of endogenous cholesterol ester and free fatty acid, and is closely associated with the pathogenesis of hepatocellular carcinoma. This review describes current developments in the molecular structure, the roles in drug, toxins and lipid metabolism, and the early diagnosis for hepatocellular carcinoma of human carboxylesterase 1.
Carboxylic Ester Hydrolases ; genetics ; physiology ; Carcinoma, Hepatocellular ; diagnosis ; Cholesterol Esters ; metabolism ; Fatty Acids, Nonesterified ; metabolism ; Humans ; Liver Neoplasms ; diagnosis ; Xenobiotics ; metabolism

OBJECTIVETo investigate the expression of special AT-rich sequence binding protein 1 (SATB1) mRNA in hepatocellular carcinoma (HCC) and explore its correlation to the clinicopathological features, surgical outcomes and metastasis of HCC.

METHODSThe total RNA was extracted from 102 HCC tissues and the adjacent tissues, and the expression of SATB1 mRNA was detected using quantitative real-time PCR. The correlations of SATB1 mRNA expression to the clinicopathological features, postoperative recurrence and metastasis of the tumor were analyzed.

RESULTSThe expression of SATB1 mRNA in HCC tissues was 3.27 folds higher than that in the adjacent tissues (P<0.001). The expression of SATB1 mRNA in HCC was associated with liver cirrhosis, AFP level, tumor size, tumor thrombi, histological differentiation, TNM classification, postoperative recurrence and metastasis (P<0.05), but not to the patients' gender, age, HbsAg positivity, HCV-Ab positivity, tumor number, or the presence of tumor encapsulation (P>0.05). In patients with significant high expression, high expression, and low expression of SATB1 mRNA, the postoperative recurrence rates were 82.68%, 0, and 0, with the 3-year survival rate of 0, 52.63%, and 100%, respectively.

CONCLUSIONSATB1 mRNA expression is associated with the postoperative recurrence and metastasis of HCC, and can be used as an indicator for predicting the recurrence and metastasis of HCC.

Aged ; Carcinoma, Hepatocellular ; genetics ; metabolism ; Female ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Male ; Matrix Attachment Region Binding Proteins ; genetics ; metabolism ; Middle Aged ; Neoplasm Metastasis ; diagnosis ; Neoplasm Recurrence, Local ; diagnosis ; RNA, Messenger ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; methods

OBJECTIVETo study the characteristics of gene expression of adrenal cortical steroid synthetase and its regulatory factor in mice with H22 liver cancer of different patterns.

METHODSSyndromes revealed in mice with H22 tumor were differentiated by quantified four diagnostic methods and syndrome differentiation, and mice with commonly encountered patterns (A: evil-toxin accumulation pattern, B: qi-deficiency pattern, C: yang-qi deficiency pattern and D: qi-yin-yang deficiency pattern) were screened out for subjecting to the study. Two batches of GeneChip Mouse Exon 1.0 ST Array detection were performed in the selected mice for detecting the gene expressions of adrenal cortical steroid synthetase and its regulatory factor, with the analysis performed put stress on the differential expressions in mice of various syndrome patterns.

RESULTSData obtained from the two batches detection showed well repeatability, in which similar genes of high or low expression emerged. The adrenal cortical steroid synthetase genes, such as Cyp11a1, Star, Cyp11b2, Cyp21a1, Hsd3b and Hsd17b were highly expressed, with few difference among the four patterns. However, Cyp11a1 was down-regulated and Cyp1b2 up-regulated in all patterns; Hsd3b1 and Cyp21a1 down-regulated in pattern A and B, but up-regulated in pattern C and D. As for the expressions of the relative regulatory factors, Cyb5b and Wnt4 were down-regulated but Fdx1, Fdxr, Hsd11b1, Por, Agt and Nr 0b1 were up-regulated in all patterns; Nr5al down-regulated in pattern A but up-regulated in other three patterns; Nr4al and Nr4a2 up-regulated in pattern A and down-regulated in the others.

CONCLUSIONSThe adrenal cortical steroid synthetase genes are rather conservative and stable in mice bearing H22 liver cancer, part of the expression might be correlated to the condition of disease and essence of syndromes, embodying the differences among different patterns in the same disease.

Adrenal Cortex ; metabolism ; Animals ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Liver Neoplasms ; diagnosis ; genetics ; metabolism ; Male ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred Strains ; Oligonucleotide Array Sequence Analysis ; Oxidoreductases ; genetics ; metabolism ; Steroids ; biosynthesis ; Yang Deficiency ; Yin Deficiency