AFP-negative Hepatocellular Carcinoma Patients Research Articles

Prognostic Significance of Alpha-fetoprotein Status in the Outcome of Hepatocellular Carcinoma after Treatment of Transarterial Chemoembolization

Alpha-fetoprotein (AFP) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its prognostic significance is not well defined. This study was performed to classify the prognostic significance of AFP status in HCC patients after transarterial chemoembolization (TACE). Four hundred forty-one HCC patients from a prospective maintained database with pathologic confirmation including 139 with normal AFP levels and 302 with elevated AFP levels were retrospectively studied for prognostic significance of AFP in treatment response and survival after TACE. Univariate and multivariate analyses were used to identify the prognostic factors. There were significant differences in overall survival (OS) after TACE between AFP-negative and AFP-positive HCC patients when the AFP cutoff value was defined as 20 ng/ml (P < 0.0001). Among the AFP-positive patients, different AFP levels had no significantly prognostic effects on OS after TACE (P = 0.093). Multivariate analysis revealed that AFP status for AFP-negative or positive was an independent prognostic factor for HCC patients after TACE (P = 0.001), along with γ-glutamyltransferase (GGT) level (P = 0.004) and tumor diameter (P < 0.0001). In addition, there were significant differences in clinicopathologic features between AFP-positive and AFP-negative patients with regard to age, gender, alanine transferase level, GGT level, tumor diameter, and Barcelona Clinic Liver Cancer stage. Compared with AFP-positive HCC patients, patients with AFP-negative status have a better treatment response and prognosis after TACE.

Diagnostic value of serum haptoglobin protein as hepatocellular carcinoma candidate marker complementary to α fetoprotein

More than 80% of hepatocellular carcinoma (HCC) arises in HBV based liver cirrhotic patients, suggesting that patients with cirrhosis form the main risk group of HCC. α fetoprotein (AFP) has poor sensitivity for the detection of AFP-negative and/or small tumors in HCC patients. Screening serum markers, along with HCC surveillance in patients with cirrhosis, can lead to the detection of HCC at an earlier stage, when curative therapy is likely to be more successful. Sera from 27 patients with HCC and 10 patients with HBV based liver cirrhosis (LC) were screened by comparative proteome analysis. Five significantly differential proteins (HP, Hp2, preprohaptoglobin, SP40 and SAA1) were identified using 2DE followed by MALDI-TOF-MS analysis. Haptoglobin (HP) was identified and found to be overexpressed in HCC as compared with LC. The result from Western blot analysis and turbidimetry detection showed serum levels of HP in HCC patients were significantly (p<0.05) higher than those in LC patients, which was consistent with the result of 2-DE. In addition, combining HP and AFP greatly improved the diagnostic accuracy (AUC=0.838). Additionally, serum HP also showed potential diagnostic value (AUC=0.763) for AFP-negative HCC patients. Altogether, it suggested that serum HP as a candidate marker complementary to α fetoprotein.

High expressions of vascular endothelial growth factor and platelet-derived endothelial cell growth factor predict poor prognosis in alpha-fetoprotein-negative hepatocellular carcinoma patients after curative resection

To evaluate the prognosis value of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients after curative resection. Tumor tissue microarrays (TMAs) were used to detect the expressions of VEGF and PD-ECGF in consecutive 162 AFP-negative HCC patients undergoing curative resection between 1997 and 2000 in our institute. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Multivariate study with Cox's proportional hazard model was used to evaluate the prognosis-related aspects. The positive rates of VEGF and PD-ECGF in tumor tissues were 59.9% (97/162) and 62.3% (101/162), respectively. Univariate analysis showed that VEGF and PD-ECGF were prognostic factors for relapse-free survival (P = 0.034 and P = 0.033, respectively). Multivariate analyses demonstrated that the co-index (VEGF/PD-ECGF) was an independent prognostic factor for overall survival and relapse-free survival (P = 0.002 and P = 0.000, respectively). The co-index of VEGF and PD-ECGF is a promising independent predictor for recurrence and survival of AFP-negative HCC patients after curative resection.

Plasma nitrite/nitrate concentrations as a tumor marker for hepatocellular carcinoma

Since plasma concentrations of nitrite/nitrate, the stable end-products of nitric oxide, increase in patients with hepatocellular carcinoma (HCC) correlatively to tumor volume, we examined the ability of plasma nitrite/nitrate to discriminate between those patients with HCC and those without and compared the diagnostic performance of the parameter with that of serum α-fetoprotein (AFP) concentrations. Plasma nitrite/nitrate and serum AFP concentrations were measured using a Griess reaction and a solid phase enzyme immunoassay, respectively. Eighty-nine patients with chronic liver diseases (CLD) with ( n=39) or without HCC ( n=50) and 50 healthy control subjects participated in the study. A receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value and accuracy. The areas under ROC curves for nitrite/nitrate and AFP were calculated to be 0.758 and 0.812, respectively, which were not significantly different. There was no correlation between the concentrations of plasma nitrite/nitrate and serum AFP. The sensitivity, the specificity, and diagnostic efficiency were 79.5, 72.0, and 75.3%, respectively, for nitrite/nitrate, and 74.4, 76.0, and 75.3%, respectively, for AFP. Based on a partial ROC curve, the clinical utility of plasma nitrite/nitrate as a tumor marker approximated that of serum AFP, but exceeded in AFP-negative patients. Indeed, nitrite/nitrate was positive in 70% of AFP-negative HCC patients. The simultaneous determinations of serum AFP and plasma nitrite/nitrate concentrations gave significant improvement in detection of HCC in CLD patients compared with that of serum AFP alone.

Clinical evaluation of a monoclonal antibody to serum KM01 for the diagnosis of hepatocellular carcinoma

In order to evaluate a monoclonal antibody KM01 which was developed in mice immunized against a human colon carcinoma cell line, serum levels of KM01 and other tumor markers were studied in patients with both hepatocellular carcinoma and liver cirrhosis and in patients with liver cirrhosis alone. The KM01 levels in the sera of 50 patients with hepatocellular carcinoma plus liver cirrhosis and 50 patients with liver cirrhosis were measured using an enzyme immunoassay method and compared with various tumor markers including α-fetoprotein (AFP), DUPAN-2,and protein induced vitamin K absence or antagonist-II (PIVKA-II). The mean serum level (±MSD.) and sensitivity of KM01 in patients with hepatocellular carcinoma plus liver cirrhosis were 734 (± 716) units/ml and 64%, respectively, they were significantly higher than those of liver cirrhosis patients ( P < 0.001). Three out of 9 cases showing negative serum AFP levels had positive serum KM01 levels. Although the sensitivity of serum KM01 level for hepatocellular carcinoma was inferior to serum AFP and plasma PIVKA-II values, the sensitivity of a combination assay of serum KM01 or AFP was increased to 88%. Clinical data of the patients with markedly elevated serum KM01 levels (more than 1000 units/ml) were compared with patients with moderately elevated levels (530–1000 units/ml); serum bilirubin and alkaline-phosphatase were statistically higher in the former group ( P < 0.01). These data suggest that the serum KM01 assay is a useful tumor marker for patients with hepatocellular carcinoma, especially in AFP negative hepatocellular carcinoma patients, and that biliary tract involvement may contribute to increased serum KM01 value.