Squamous cell carcinoma antigen-immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma

Cancer. 2005 Jun 15;103(12):2558-65. doi: 10.1002/cncr.21106.


Background: Early detection of hepatocellular carcinoma (HCC), one of the most common and deadly tumors worldwide, still is difficult due to the lack of adequate biomarkers that show high sensitivity and specificity. The authors recently demonstrated that squamous cell carcinoma antigen (SCCA) variants were overexpressed remarkably in all surgically resected HCCs.

Methods: For the current study, the authors assessed the presence of SCCA, as a free form and complexed with immunoglobulins, in serum from patients with HCC, cirrhosis, and chronic hepatitis and from healthy control participants and compared SCCA measurement with the measurement of alpha-fetoprotein (AFP) levels.

Results: Circulating immune complexes (ICs) composed by SCCA and immunoglobulin M (IgM) IC (SCCA-IgM IC) were undetectable (< 120 arbitrary units [AU]/mL) in serum from a healthy control population (0 of 73 controls); however, 35 of 50 patients with HCC (70%) were reactive for SCCA-IgM IC independent of etiology (mean +/- standard deviation [SD], 2568.5 +/- 6797.3 AU/mL). No correlation was found with AFP levels, which were elevated significantly in only 21 of 50 patients with HCC (42%). By using an AFP cut-off value of 20 ng/mL, 96% of patients with HCC were positive for at least 1 marker. Among cirrhotic patients, the presence of circulating SCCA-IgM IC was displayed in 13 of 50 patients (26%), but at lower levels compared with the patients who had HCC (mean +/- SD, 147.5 +/- 348.3 AU/mL; P < 0.01; Student t test), whereas 9 of 50 patients with chronic hepatitis (18%) were reactive (mean +/- SD, 39.5 +/- 89.7 AU/mL). No significant presence of free SCCA, free anti-SCCA variants IgG or IgM, or SCCA-IgG IC was found.

Conclusions: The study results indicated that SCCA-IgM ICs represent novel serologic biomarkers, which, alone or in combination with AFP, can increase the sensitivity for diagnosing HCC significantly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / blood*
  • Antigens, Neoplasm / chemistry
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / chemistry
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / chemistry
  • Carcinoma, Hepatocellular / diagnosis*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatitis, Chronic / blood
  • Hepatitis, Chronic / diagnosis
  • Humans
  • Immunoglobulin M / blood*
  • Immunoglobulin M / chemistry
  • Liver / metabolism
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis
  • Liver Neoplasms / blood
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / diagnosis
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Serpins / blood*
  • Serpins / chemistry
  • alpha-Fetoproteins / metabolism


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Immunoglobulin M
  • Serpins
  • alpha-Fetoproteins
  • squamous cell carcinoma-related antigen