Isoelectric focusing of alphafetoprotein in patients with hepatocellular carcinoma-frequency of specific banding patterns at non-diagnostic serum levels

Serum levels of alphafetoprotein are raised in 60-80% of patients with hepatocellular carcinoma. Although widely used as a serum marker, frequent false-positive results in patients with benign liver disease, result in poor specificity. This occurs particularly when levels of alphafetoprotein fall between 50-500 ng ml-1, the so-called 'grey area'. Recent reports suggest that isoelectric focusing of alphafetoprotein demonstrates certain bands that are more specific for hepatocellular carcinoma. Our aim was to determine whether the apparent specificity of this new approach is gained at the expense of decreased sensitivity. Sera from 110 patients with a 'non-diagnostic' serum alphafetoprotein level (50-500 ng ml-1) were examined by isoelectric focusing and quantified by densitometric scanning. Ten patients with chronic liver disease and a raised serum alphafetoprotein level (50-500 ng ml-1), but with no evidence of hepatocellular carcinoma, were also studied. Isoelectric focusing revealed characteristic hepatocellular carcinoma bands (bands +II and +III) in 96% patients overall, and 100% of those with levels of total alphafetoprotein greater than 100 ng ml-1. No such bands were seen among ten subjects with cirrhosis but without hepatocellular carcinoma. Bands that are characteristic of hepatocellular carcinoma (bands +II or +III) are seen in the great majority of hepatocellular carcinoma patients; their absence makes a diagnosis of hepatocellular carcinoma extremely unlikely.