Serum tumor markers in patients with hepatocellular carcinoma: diagnosis of alpha-fetoprotein -low or -negative patients.

The presence of specific gamma-glutamyl transpeptidase isoenzyme (gamma-GTPI) and variant alkaline phosphatase (VAALP) were concurrently determined, and levels of basic fetoprotein (BFP) and carcinoembryonic antigen (CEA) in addition to alpha-fetoprotein (AFP) were measured in 144 hepatocellular carcinoma (HCC) patients in order to evaluate the diagnostic value of these tumor markers with respect to AFP-low or -negative patients and the tumor stage. Serum AFP levels below 400 ng/ml, commonly seen in sera of hepatobiliary diseases other than HCC, were noted in 42% of the patients. The diagnostic usefulness was increased by combination assay of these markers except for CEA. A definitive diagnosis of HCC could be made in 78% of the patients by a combination of gamma-GTPI, VAALP and AFP. Moreover, a diagnosis of malignancy could be made in 87% of cases by the inclusion of BFP. The prevalence of BFP and CEA increased in proportion to the tumor stage, whereas that of AFP and gamma-GTPI were independent of stage and were high even in patients in comparatively early stages. Furthermore, secreting type markers such as AFP and gamma-GTPI were relatively useful for diagnosis of HCC when the lesions were still small.