Alpha-Fetoprotein (AFP) L3% and Total, Hepatocellular Carcinoma Tumor Marker, Serum

CPT CODE:

USEFUL FOR:

Distinguishing between hepatocellular carcinoma and chronic liver disease
Monitoring individuals with hepatic cirrhosis from any etiology for progression to hepatocellular carcinoma
Surveillance for development of hepatocellular carcinoma in individuals with a positive family history of hepatic cancer
Surveillance for development of hepatocellular carcinoma inindividuals within specific ethnic and gender groups who do nothave hepatic cirrhosis, but have a confirmed diagnosis of chronicinfection by hepatitis B acquired early in life including: - African males above the age of 20 - Asian males above the age of 40 - Asian females above the age of 50

SPECIMEN REQUIRED:

Draw blood in a plain, red-top tube(s). Spin down, and send 0.5 mL of serum frozen in plastic vial.

TRANSPORT TEMPERATURE:

Frozen\Refrig <6 days OK\Ambient NO(avoid temperature extremes)

CLINICAL INFORMATION:

Worldwide, hepatocellular carcinoma is the third leading cause of death from cancer.(1) While hepatocellular carcinoma can be treated effectively in its early stages, most patients are not diagnosed untilthey are symptomatic and at higher grades and stages, which are less responsive to therapies. Alpha-fetoprotein (AFP) is the standard serum tumor marker utilized in the evaluation of suspected hepato-cellular carcinoma. However, increased serum concentrations of AFPmight be found in chronic hepatitis and liver cirrhosis, as well as inother tumor types (e.g., germ cell tumors[2]), decreasing the specificityof AFP testing for hepatocellular carcinoma. Furthermore, AFP is notexpressed at high levels in all hepatocellular carcinoma patients,resulting in decreased sensitivity, especially in potentially curablesmall tumors.
AFP is differentially glycosylated in several hepatic diseases. Forexample, UDP-alpha-1g6-fucosyltransferase is differentiallyexpressed in hepatocytes following malignant transformation.(3) This enzyme incorporates fucose residues on the carbohydrate chains of AFP. Different glycosylated forms of AFP can be recognized following electrophoresis by reaction with different carbohydrate-binding plant lectins. The fucosylated form of serum AFP that is most closely associated with hepatocellular carcinomais recognized by a lectin from the common lentil (Lens culinaris). This is designated as AFP-L3 (third electrophoretic form of lentil lectin-reactive AFP). AFP-L3 is most useful in the differential diagnosis of individuals with total serum AFP < or = 200 ng/mL,which may result from a variety of benign pathologies, such aschronic liver diseases.
AFP-L3 should be utilized as an adjunct to high-resolution ultrasoundfor surveillance of individuals at significant risk for developing hepaticlesions, as described below.

CLINICAL INTERPRETATION:

Total serum AFP > 200 ng/mL is highly suggestive of a positivediagnosis of hepatocellular carcinoma. In patients with liver disease,a total serum AFP of >200 ng/mL is near 100% predictive of hepato-cellular carcinoma. With decreasing total AFP levels, there is anincreased likelihood that chronic liver disease, rather than hepatocellular carcinoma, is responsible for the AFP elevation.
For patients with total AFP levels < or = 200 ng/mL, the ratio of theAFP-L3 to the total AFP is predictive of the presence of hepato-cellular carcinoma, including a very small preclinical hepatocellularcarcinoma. In this group of patients, the positive predictive valueand specificity of AFP-L3 approaches 100% for hepatocellularcarcinoma when its percentage exceeds 35% of the total AFP.(4)
The specificity of AFP-L3 decreases to approximately 63% as the percentage of AFP-L3 decreases from 35% to 10%. Either chronic liver disease or hepatocellular carcinoma is possible in these cases and additional clinical findings are necessary to obtain a diagnosis.
AFP-L3 > or = 10% is associated with a 7-fold increased risk ofdeveloping hepatocellular carcinoma. Patients with AFP-L3 > or = 10%should be monitored more intensely for evidence  of hepatocellularcarcinoma following current practice guidelines.
This test provides no diagnostic information when either the total AFP is <10 ng/mL or AFP-L3 is <10%. These results may beseen in either normal subjects or patients with hepatocellularcarcinoma or chronic liver diseases.
The data shown in "Reference Values" lists the decision making levelsestablished in a retrospective study at the Mayo Clinic. (see SupportiveData). Diagnostic cutoffs may differ slightly in other patient populations.

REFERENCE VALUES:

TOTAL %L3AFP

                *Percent AFP-L3/total AFP values were determined in a retrospective

                 clinical study (Leerapun A, Suravarapu S, Bida JP, et al: The utility of