title: Clinical validation of combined serological biomarkers for improved hepatocellular carcinoma diagnosis in 961 patients.
abstract: BACKGROUND
  Alpha-fetoprotein (AFP), the only serological marker currently available for the detection of hepatocellular carcinoma (HCC), is unsatisfactory because of its poor sensitivity, as are other recently proposed markers. Therefore new biomarkers are badly needed. Squamous cell carcinoma antigen (SCCA), a serine protease inhibitor physiologically present in the skin, has recently been reported to be present in HCC patients, as also the immunocomplexed (IC) forms of SCCA and AFP: SCCAIC and AFPIC, respectively.
  
  
  METHODS
  To determine the diagnostic accuracy of new serum biomarkers for the diagnosis of HCC a rapid, simple ELISA test was applied in 961 patients. Sensitivity and specificity were determined for each marker and for all the markers combined in detecting smaller and larger HCC versus liver cirrhosis.
  
  
  RESULTS
  In smaller HCC, receiver operating characteristics analysis yielded the following AUC: AFP 0.714 (CI 95% 0.679-0.748), AFPIC 0.691 (CI95% 0.655-0.748), SCCA 0.703 (CI95% 0.667-0.736), SCCAIC 0.694 (CI 95% 0.659-0.728). SCCA was inversely correlated with size. The combined use of AFPIC, SCCA and SCCAIC in patients displaying low levels of AFP (<20 IU/mL) identified 25.6% HCC (186/725).
  
  
  CONCLUSIONS
  This study suggests that the use of a combination of all these markers in clinical practice provides a non invasive and simple test that could increase the accuracy of HCC diagnosis.
authors.affiliation: Department of Internal Medicine, Immunology and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Bari, Italy. g.giannelli@intmed.uniba.it
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Giannelli
authors.forename: Emilia
authors.initials: E
authors.lastname: Fransvea
authors.forename: Paolo
authors.initials: P
authors.lastname: Trerotoli
authors.forename: Michel
authors.initials: M
authors.lastname: Beaugrand
authors.forename: Felice
authors.initials: F
authors.lastname: Marinosci
authors.forename: Luigi
authors.initials: L
authors.lastname: Lupo
authors.forename: Gisele
authors.initials: G
authors.lastname: Nkontchou
authors.forename: Pietro
authors.initials: P
authors.lastname: Dentico
authors.forename: Salvatore
authors.initials: S
authors.lastname: Antonaci
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D019937:Diagnostic Techniques and Procedures; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D015843:Serpins / Q000097:blood*; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015843:Serpins; D000509:alpha-Fetoproteins; C051072:squamous cell carcinoma-related antigen