Culinaris Agglutinin-reactive Fraction Of Alpha-fetoprotein Research Articles

Prognostic Significance of Simultaneous Measurement of Three Tumor Markers in Patients With Hepatocellular Carcinoma

We conducted a prospective study to evaluate the significance of simultaneous measurement of 3 currently used tumor markers in the evaluation of tumor progression and prognosis of patients with hepatocellular carcinoma (HCC). Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), were measured in the same serum samples obtained from 685 patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL, AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition, tumor markers were measured after treatment of HCC. Of the 685 patients, 337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371 (54.2%) were positive for DCP. In a comparison of patients positive for only 1 tumor marker, patients positive for AFP-L3 alone had a greater number of tumors, whereas patients positive for DCP alone had larger tumors and a higher prevalence of portal vein invasion. When patients were compared according to the number of tumor markers present, the number of markers present clearly reflected the extent of HCC and patient outcomes. The number of markers present significantly decreased after treatment. Tumor markers AFP-L3 and DCP appear to represent different features of tumor progression in patients with HCC. The number of tumor markers present could be useful for the evaluation of tumor progression, prediction of patient outcome, and treatment efficacy.

Usefulness of the Novel Oncofetal Antigen Glypican-3 for Diagnosis of Hepatocellular Carcinoma and Melanoma

Glypican-3 (GPC3) mRNA and protein are expressed in >80% of human hepatocellular carcinomas (HCC) but not in normal tissues except for placenta and fetal liver. The oncofetal antigen GPC3 is a glycosylphosphatidyl inositol-anchored membrane protein and may be secreted. It is a novel tumor marker for human HCC: GPC3 protein was present in sera from 40-50% of HCC patients, but was not detected in sera from patients with liver cirrhosis or chronic hepatitis, or in sera from healthy individuals. alpha-Fetoprotein (AFP) and PIVKA-II (protein induced by vitamin K absence or antagonist-II), are well known major tumor markers for HCC. Generally, AFP shows high positivity for HCC but also high false-positivity in detection assays. Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) is a recently described marker of HCC. Detection of AFP-L3 shows a much higher specificity than AFP, but a lower sensitivity. On the other hand, detection of PIVKA-II shows a lower false-positivity, but is not always sensitive enough to detect low levels secreted by small HCCs. There was no correlation between the three tumor markers, AFP, PIVKA-II, and GPC3 in terms of their presence in HCC cells. All three tumor markers showed similar positivity in patients with HCC, detecting 80% of patients with the disease. GPC3 is also a novel tumor marker for the diagnosis of human melanoma, especially in the early stages of the disease. Expression of GPC3 mRNA and protein was evident in tumor cells from >80% of patients with melanoma and melanocytic nevus, which is a common benign lesion. GPC3 protein was detected in sera from 40% (36/91) of melanoma patients, but not in sera from those with large congenital melanocytic nevus, or from healthy donors. Surprisingly, we detected serum GPC3 even in patients with stage 0, in situ melanoma. The positive detection rate of serum GPC3 at stage 0, I, and II (44.4%, 40.0%, 47.6%, respectively) was significantly higher than that of 5-S-cysteinyldopa, a well known tumor marker for melanoma (0.0%, 8.0%, and 10.0%, respectively). Interestingly, GPC3 was highly immunogenic in mice and elicited effective anti-tumor immunity with no evidence of autoimmunity. Thus, GPC3 is useful for diagnosis of HCC and melanoma and may also have a role in immunotherapy or tumor prevention. However, studies in humans are warranted.

Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein.

The Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) has been reported to be a highly useful marker for hepatocellular carcinoma (HCC) compared with a conventional serum AFP concentration, which allows earlier detection of HCC compared with using other imaging modalities and predicting prognosis after therapy. A collaborative prospective study involving nine Japanese hospitals was conducted to analyze the relationships between the tumor characteristics of a HCC patient and the percentage of AFP-L3/AFP total at the initial detection. Between 1 October 1996 and 30 September 1997, a total of 388 patients with newly diagnosed HCC were registered. The cut-off level of the percentage of AFP-L3 was altered from 15 to 10%. The AFP-L3-positive HCC patients demonstrated the characteristics of having an advanced tumor, such as the number of tumors, maximum diameter, tumor spread, portal vein invasion, tumor stage, and tumor classification. With the conventional cut-off level of 15% of the percentage of AFP-L3, the malignant characteristics were more definite than that of 10%. However, no significant differences of serum AFP concentration were observed for malignant characteristics such as maximum diameter and histopathological grading. Serum AFP concentration does not reveal a malignancy of HCC, however, the AFP-L3-positive HCC has biologically malignant characteristics, especially portal vein invasion and lower tumor classification, and is an advanced tumor regardless of small tumor size and lower serum AFP concentration. As AFP-L3 shows the tumor characteristics, its presence should be an important factor in the determination of therapy and prognosis of patients.

Usefulness of measurement of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein as a marker of prognosis and recurrence of small hepatocellular carcinoma.

Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3%) is a recently described marker of hepatocellular carcinoma (HCC), and its usefulness has been demonstrated in many studies. We evaluated the usefulness of serial measurement of AFP-L3% as a marker of prognosis and recurrence after treatment of small HCC. AFP-L3% was measured before and after initial treatment in 60 patients with small HCC (maximum diameter < or = 2 cm). AFP-L3% was taken as the ratio of AFP-L3 to total AFP and multiplied by 100%, and levels > or = 10% were considered positive. Outcomes and recurrence were compared between patients AFP-L3%-negative after initial treatment (Group A, n = 43) and patients who were AFP-L3%-positive after initial treatment (Group B, n = 17). Before treatment, AFP-L3% was positive in 14 (23.3%) of the 60 patients. The cumulative survival rate of Group A was significantly longer (p = 0.0091) than that of Group B. The recurrence rate was significantly higher in Group B (p = 0.0104) than in Group A. When recurrence was limited to intrahepatic metastasis, the recurrence rate was significantly higher in Group B (p = 0.0064). However, the recurrence rate of multicentric occurrence did not differ significantly between Groups A and B. Measurement of AFP-L3% after treatment may be useful for understanding prognosis and recurrence of HCC.

Serum alpha-fetoprotein and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein in patients with hepatocellular carcinoma.

A fraction of serum alpha-fetoprotein (AFP) reactive with lens culinaris agglutinin (LCA) was measured by affinity chromatography in serum samples from 102 patients with hepatocellular carcinoma (HCC) and 48 patients with chronic liver diseases without HCC. Its usefulness as a marker of HCC was evaluated. The mean +/- SD percentage of this fraction in total AFP was 3.10 +/- 3.17% in 48 patients with chronic liver diseases without HCC. When the cut-off level was set at 12.6% (mean + 3 SD), the sensitivity was 36.3%, the specificity was 100%, and the accuracy was 56.7% in the 102 patients with HCC. This lentil lectin-reactive AFP was positive in 7 of 25 patients (28%) who had single small liver cancer (phi < 20 mm), suggesting its clinical usefulness as a tumor marker. The lentil lectin-reactive AFP showed no correlation with the serum concentration of AFP or des-gamma-carboxy prothrombin (DCP). In patients with HCC showing an AFP level of 20 ng/ml or above, the lentil lectin-reactive fraction is a highly specific tumor marker. We consider it to be useful as an adjunct in the diagnosis of HCC.