Hepatocellular carcinomas (HCCs) show genomic alterations, including DNA rearrangements associated with HBV DNA integration, loss of heterozygosity, and chromosomal amplification. The genes most frequently involved are those encoding tumor suppressors. The p16INK4A tumor suppressor gene frequently displays genetic alteration in HCC tissues. The present study was performed to examine the incidence of methylated p16INK4A in the sera of liver cirrhosis (LC) and HCC patients, and to evaluate its role as a tumor marker of HCC. The sera of 23 LC patients and 46 HCC patients were examined in this study. The methylation status of p16INK4A was evaluated by methylation-specific PCR of serum samples. Methylated p16INK4A was detected in 17.4% (4/23) of LC patients and in 47.8% (22/46) of HCC patients. No association was demonstrated between p16INK4A methylation and serum AFP level. As the status of p16INK4A methylation was not associated with serum AFP level, it may have a role as a tumor marker of HCC.
Aged ; Carcinoma, Hepatocellular/*genetics ; DNA/metabolism ; *DNA Methylation ; Female ; Fibrosis ; *Genes, p16 ; Human ; Liver/pathology ; Liver Cirrhosis/*genetics ; Liver Neoplasms/*genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Predictive Value of Tests ; Protein p16/*blood ; Sensitivity and Specificity ; Time Factors ; Tumor Markers, Biological

BACKGROUND: Tissue factor (TF) is a main physiological initiator of blood coagulation and may be important in the biology of a variety of solid malignancies, particularly where angiogenesis is a critical factor. In liver cirrhosis, hyperfibrinolysis is frequently observed in patients with the decompensated state and which may be secondary to the increased production of thrombin. Many studies have shown that the expression of TF in tumors contributes not only to tumor-derived procoagulant activity but also to hematogenous metastasis and tumor angiogenesis. The aim of this study was to evaluate how plasma TF concentration was correlated with the severity of liver cirrhosis and the progression of hepatocellular carcinoma. METHODS: This study consisted of 23 patients with liver cirrhosis (LC) and 37 patients with hepatocellular carcinoma (HCC). HCC patients was graded by TNM staging system of The Union Internationale Contre le Cancer (UICC). Plasma TF concentration was measured by the enzyme linked immunosorbent assay (ELISA). The severity of the liver disease was estimated by Child-Pugh classification. The correlation of TF concentration in patients with LC and HCC in diffenrent classifications was evaluated. RESULTS: There was no difference between LC and HCC in the plasma TF concentration (p=0.236). The TF concentration was different according to Child-Pugh score (p=0.024) and proportion to Child-Pugh score in class B and C (p<0.05). The TF concentration of HCC patients was not different between the classes of severity of underlying LC and the TF concentration of stage IVA was higher than that of stage I, II, III in HCC patients (p=0.039). CONCLUSION: The plasma concentration of TF was correlated with the degree of severity of liver disease in cirrhotic patients and increased in the advanced stages of HCC.
Biology ; Blood Coagulation ; Carcinoma, Hepatocellular* ; Classification ; Enzyme-Linked Immunosorbent Assay ; Humans ; Liver Cirrhosis* ; Liver Diseases ; Liver* ; Neoplasm Metastasis ; Neoplasm Staging ; Plasma* ; Thrombin ; Thromboplastin*

BACKGROUND: CDX1 and CDX2, members of the caudal-type homeobox gene family, control proliferation and differentiation of intestinal mucosal cells. Their expression is reduced commonly in colorectal cancers, but reports about the relationship between their expression and the clinicopathologic features are rare. The aim of this study was to examine CDX1 mRNA and CDX2 mRNA expression in colorectal cancers and to assess the relationship between their expression and the clinicopathologic features. METHODS: CDX1 mRNA and CDX2 mRNA expression were analyzed by real-time polymerase chain reaction in 48 colorectal cancers and their adjacent non-tumorous normal mucosas. RESULTS: CDX1 mRNA and CDX2 mRNA expression were decreased significantly in colorectal cancers than in normal mucosas (p=0.001, p=0.042, respectively). In comparison with paired normal mucosas, colorectal cancers showed decreased CDX1 mRNA expression in 64.6% (31/48) and decreased CDX2 mRNA expression in 66.7% (32/48). There was a statistically significant correlation between CDX1 mRNA and CDX2 mRNA expression in colorectal cancers (r=0.543, p<0.001). CDX1 mRNA and CDX2 mRNA expression were not related to age, sex, location of cancer, differentiation, lymphatic or vascular invasion, lymph node metastasis, stage and serum carcinoembryonic antigen level in colorectal cancers. CONCLUSION: CDX1 mRNA and CDX2 mRNA expression were decreased significantly in colorectal cancers, but were not related to the clininopathologic features.
Carcinoembryonic Antigen ; Colorectal Neoplasms* ; Genes, Homeobox ; Humans ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis ; Real-Time Polymerase Chain Reaction ; RNA, Messenger*

BACKGROUND: CDX1 and CDX2 are members of the caudal-type homeobox gene family and control the proliferation and differentiation of intestinal mucosal cells. Their expressions are commonly reduced in colorectal cancer, but reports about the relationships between their expressions and clinicopathologic features are rare. The aim of this study was to examine the expressions of CDX1 and CDX2 mRNAs in colorectal cancers and to assess the relationships between their expressions and clinicopathologic features. METHODS: CDX1 and CDX2 mRNA expressions were analyzed by real-time polymerase chain reaction in 48 colorectal cancers and in adjacent non-tumorous normal mucosal tissue. RESULTS: CDX1 and CDX2 mRNA expressions were significantly reduced in colorectal cancer tissues versus normal mucosal tissues (p=0.001, p=0.042, respectively). As compared with paired normal mucosal tissues, colorectal tissues showed reduced CDX1 mRNA expression in 64.6% (31/48) and reduced CDX2 mRNA expression in 66.7% (32/48) of cases. A statistically significant positive correlation was found between the expressions of CDX1 mRNA and CDX2 mRNA in colorectal cancer (r=0.543, p< 0.001). However, the expressions of CDX1 and CDX2 mRNAs were not related to age, sex, cancer location, differentiation, lymphatic or vascular invasion, lymph node metastasis, stage or serum carcinoembryonic antigen level. CONCLUSIONS: CDX1 and CDX2 mRNA expressions were found to be significantly reduced in colorectal cancers, but these expressional changes were not found to be related to clinicopathologic features.
RNA, Messenger/*metabolism ; Polymerase Chain Reaction ; Middle Aged ; Male ; Humans ; Homeodomain Proteins/*metabolism ; Female ; Colorectal Neoplasms/*metabolism