title: Cancer antigen 125, human epididymis 4, kallikrein 6, osteopontin and soluble mesothelin-related peptide immunocomplexed with immunoglobulin M in epithelial ovarian cancer diagnosis.
abstract: BACKGROUND
  Human epididymis protein 4 (HE4), kallikrein 6 (KLK6), osteopontin (OPN) and soluble mesothelin-related peptide (SMRP) are new promising biomarkers that could integrate CA125 in epithelial ovarian cancer (EOC) diagnosis. The autoantibody response to tumor antigens is a potential tool for improving the diagnostic performances of biomarkers. The aim of this study was to assess the diagnostic potential of these biomarkers in the form of free markers and immunocomplexed with immunoglobulin M (IgM). Moreover, we analyzed the association between these markers and clinico-pathological characteristics of EOC patients.
  
  
  METHODS
  Serum and plasma samples of 60 healthy controls, 60 ovarian benign cysts, 60 endometriosis and 60 EOCs, collected before any treatment, were tested for CICs and free antigens by immunoassays.
  
  
  RESULTS
  Immunocomplexes were characterized by poor sensitivity and specificity, since they allowed the detection only of a small number of EOC patients and were increased in patients with benign gynecological pathologies. However, the markers in the form of free antigens showed good diagnostic performances. Of note, CA125 and HE4 showed high sensitivity in the detection of the malignancy and HE4 emerged as a useful biomarker in differential diagnosis between EOC and endometriosis. Finally, elevated KLK6 and OPN, were associated with advanced FIGO stage, high grade disease, suboptimally debulked tumor and ascites.
  
  
  CONCLUSIONS
  This study confirms the diagnostic role of CA125, HE4, KLK6, OPN and SMRP, and for the first time showed that CA125, HE4, KLK6, OPN and SMRP immunocomplexed with IgM are not a potential tool for EOC diagnosis.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bandiera
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.forename: Aline S C
authors.initials: AS
authors.lastname: Fabricio
authors.forename: Elisa
authors.initials: E
authors.lastname: Bucca
authors.forename: Elisa
authors.initials: E
authors.lastname: Squarcina
authors.forename: Chiara
authors.initials: C
authors.lastname: Romani
authors.forename: Renata
authors.initials: R
authors.lastname: Tassi
authors.forename: Eliana
authors.initials: E
authors.lastname: Bignotti
authors.forename: Paola
authors.initials: P
authors.lastname: Todeschini
authors.forename: Germana
authors.initials: G
authors.lastname: Tognon
authors.forename: Cesare
authors.initials: C
authors.lastname: Romagnolo
authors.forename: Massimo
authors.initials: M
authors.lastname: Gion
authors.forename: Enrico
authors.initials: E
authors.lastname: Sartori
authors.forename: Tiziano
authors.initials: T
authors.lastname: Maggino
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Ravaggi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D018394:CA-125 Antigen / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D018796:Immunoconjugates / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D007610:Kallikreins / Q000097:blood / Q000737:chemistry / Q000276:immunology; D008297:Male; D000090204:Mesothelin; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis; D053495:Osteopontin / Q000097:blood / Q000737:chemistry / Q000276:immunology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000276:immunology; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D058851:GPI-Linked Proteins; D018796:Immunoconjugates; D007075:Immunoglobulin M; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; D053495:Osteopontin; C103551:KLK6 protein, human; D007610:Kallikreins; D000090204:Mesothelin