Beneduce L et al. (2005) Squamous cell carcinoma antigen–immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma. Cancer 103: 2558–2565

High mortality rates for hepatocellular carcinoma (HCC) and the increased prevalence of causative factors, such as chronic hepatitis and cirrhosis, have elicited a search for novel biomarkers with improved specificity and sensitivity in the early detection of HCC. Beneduce et al. have recently developed ELISA assays to compare the diagnostic accuracy of squamous cell carcinoma antigen (SCCA) variants, identified as being overexpressed in the livers of patients with HCC, with α-fetoprotein (AFP), currently the biomarker most widely used in the detection of HCC.

The serum from 73 healthy volunteers and 160 patients with various liver diseases, including 50 with HCC, were analyzed for the presence of SCCA, as free protein and in complex with immunoglobulins. Histologic analysis of liver biopsies was also performed for a subset of patients and healthy controls. SCCA–IgM complexes were detected in 70% of patients with HCC, but were undetectable in any of the healthy subjects. This result was matched by SCCA overexpression in the liver samples of patients with HCC (93% were reactive). The accuracy of SCCA–IgM complexes in discriminating between HCC and both chronic hepatitis and cirrhosis was higher than that of AFP. Free SCCA, anti-SCCA IgMs or IgGs, and SCCA–IgG complexes, were not found to be significantly elevated in patients with HCC, however. The authors concluded that SCCA–IgM complexes can significantly increase the sensitivity of diagnosis for HCC in at-risk patients.