Combined serum hepatoma-speciifc alpha-fetoprotein and circulating alpha-fetoprotein-mRNA in diagnosis of hepatocellular carcinoma

摘要

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, its prognosis is poor, and early detection is of utmost importance. Although alpha-fetoprotein (AFP) is a useful marker for detecting and monitoring HCC development, the false-negative or false-positive rates with AFP alone may be as high as 30%-40%for patients with small HCCs. To enhance the speciifcity and accuracy of AFP measurements for HCC, we analyzed AFP expression states in livers, detected the hepatoma-speciifc AFP (HS-AFP) fraction and AFP-mRNA from peripheral blood mononuclear cells, and explored their clinical implications for HCC diagnosis. METHODS:AFP expression and hepatocyte distributions in liver specimens were investigated by an immunohistoche-mical assay. Total RNAs were extracted from circulating blood, synthesized to cDNA through random primers and reverse transcriptase, and fragments of the AFP gene were ampliifed by a nested-PCR assay. The HS-AFP fraction was separated by lectin-afifnity chromatography and its level was detected by radioimmunoassay. RESULTS: The incidence of AFP was 73.3% in HCC tissues and its expression in HCCs with moderate or low differentiation was signiifcantly stronger than that of HCCs with high differentiation (P<0.05). The incidence of AFP gene fragments was 100% in HCCs, and 60% in paracancerous tissues (P<0.01). In the HCC and liver cirrhosis groups, the incidence of HS-AFP was 91.7%and 18% (P<0.01), and of AFP-mRNA was 56.7% and 16%(P<0.01), respectively, and neither was found in controls. HS-AFP or AFP-mRNA was not signiifcantly related to size or number of HCC, but to its differentiation, metastasis, and relapse (P<0.05). CONCLUSIONS: Different AFP expression is present in different parts of HCC tissues. HS-AFP and AFP-mRNA fragments improve sensitivity and speciifcity, and both are useful markers to diagnose HCC or monitor metastasis and relapse.