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.
The authors thank all the nurses working in the Department of Obstetrics and Gynaecology of University of Brescia and of the “Dell’Angelo Hospital”, Mestre-Venice, and especially Ms. Margherita Franzoni and Marta Perin, for their assistance in collecting blood samples. They also thank the staff of the Laboratory Analysis Unit, Department of Clinical Pathology, Azienda ULSS 12 Veneziana, Mestre-Venice, and especially Ms. Silvia Busnardi, Ms. Maria Cristina Perdon, Mr. Dino Tamai and Mr. Claudio Zanette, for their technical assistance in processing samples.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: Supported by grants from the Nocivelli Foundation, Brescia, Italy and by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca, Italy: PRIN project, prot2008AZJM9E and Integrated Project ‘Progetto Oncologico di Medicina Molecolare: Tumori Femminili’.
Employment or leadership: None declared.
Honorarium: None declared.
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