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.
BACKGROUND:Humanepididymis 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: Renée T Fortner; Helena Schock; Charlotte Le Cornet; Anika Hüsing; Allison F Vitonis; Theron S Johnson; Raina N Fichorova; Titilayo Fashemi; Hidemi S Yamamoto; Anne Tjønneland; Louise Hansen; Kim Overvad; Marie-Christine Boutron-Ruault; Marina Kvaskoff; Gianluca Severi; Heiner Boeing; Antonia Trichopoulou; Eleni-Maria Papatesta; Carlo La Vecchia; Domenico Palli; Sabina Sieri; Rosario Tumino; Carlotta Sacerdote; Amalia Mattiello; N Charlotte Onland-Moret; Petra H Peeters; H B As Bueno-de-Mesquita; Elisabete Weiderpass; J Ramón Quirós; Eric J Duell; Maria-Jose Sánchez; Carmen Navarro; Eva Ardanaz; Nerea Larrañaga; Björn Nodin; Karin Jirström; Annika Idahl; Eva Lundin; Kay-Tee Khaw; Ruth C Travis; Marc Gunter; Mattias Johansson; Laure Dossus; Melissa A Merritt; Elio Riboli; Kathryn L Terry; Daniel W Cramer; Rudolf Kaaks Journal: Int J Cancer Date: 2017-12-11 Impact factor: 7.396