title: Experimental validation of specificity of the squamous cell carcinoma antigen-immunoglobulin M (SCCA-IgM) assay in patients with cirrhosis.
abstract: BACKGROUND
  Squamous cell carcinoma antigen-immunoglobulin M (SCCA-IgM) is a useful biomarker for the risk of development of hepatocellular carcinoma (HCC) in patients with cirrhosis due to its progressive increase associated to HCC evolution. In patients with cirrhosis, other assays have been affected by interfering reactivities of IgM. In this study, the analytical specificity of the SCCA-IgM assay was assessed by evaluating SCCA-IgM measurement dependence on different capture phases, and by measuring the recovery of SCCA-IgM reactivity following serum fractionation.
  
  
  METHODS
  Serum samples from 82 patients with cirrhosis were analyzed. SCCA-IgM was measured using the reference test (Hepa-IC, Xeptagen, Italy) that is based on rabbit oligoclonal anti-squamous cell carcinoma antigen (SCCA) and a dedicated ELISA with a mouse monoclonal anti-SCCA as the capture antibody.
  
  
  RESULTS
  SCCA-IgM concentrations measured with the reference assay (median value=87 AU/mL) were higher than those measured with the mouse monoclonal test (median value=78 AU/mL). However, the differences in the SCCA-IgM distribution were not statistically significant (p>0.05). When SCCA-IgM concentrations measured with both tests were compared, a linear correlation was found (r=0.77, p<0.05). Fractionation of the most reactive sera by gel-filtration chromatography showed that total recovery of SCCA-IgM reactivity was seen only in the fractions corresponding to components with a molecular weight higher than IgM and SCCA (>2000 kDa) with both tests.
  
  
  CONCLUSIONS
  The equivalence of both SCCA-IgM assays and the absence of reactivity not related to immune complexes support the analytical specificity of SCCA-IgM measurements. The results validate the assessment of SCCA-IgM for prognostic purposes in patients with cirrhosis.
authors.affiliation: Xeptagen SpA, Marghera, Venice, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Zuin
authors.forename: Gianluca
authors.initials: G
authors.lastname: Veggiani
authors.forename: Paolo
authors.initials: P
authors.lastname: Pengo
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallotta
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biasiolo
authors.forename: Natascia
authors.initials: N
authors.lastname: Tono
authors.forename: Angelo
authors.initials: A
authors.lastname: Gatta
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pontisso
authors.forename: Radovan
authors.initials: R
authors.lastname: Toth
authors.forename: Dean
authors.initials: D
authors.lastname: Cerin
authors.forename: Vladimir
authors.initials: V
authors.lastname: Frecer
authors.forename: Sabrina
authors.initials: S
authors.lastname: Meo
authors.forename: Massimo
authors.initials: M
authors.lastname: Gion
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fassina
authors.forename: Luca
authors.initials: L
authors.lastname: Beneduce
mesh_terms: D000368:Aged; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology; D001681:Biological Assay; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis; D002850:Chromatography, Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D011379:Prognosis; D012680:Sensitivity and Specificity; D015843:Serpins / Q000097:blood* / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D007075:Immunoglobulin M; D015843:Serpins; C051072:squamous cell carcinoma-related antigen