Abstract
BackgroundEpithelial ovarian cancer is one of the leading causes of gynaecological cancer morbidity and mortality in women. Early stage ovarian cancer is usually asymptomatic, therefore, is often first diagnosed when it is widely disseminated. Currently available diagnostics lack the requisite sensitivity and specificity to be implemented as community-based screening tests. The identification of additional biomarkers may improve the diagnostic efficiency of multivariate index assays. The aims of this study were to characterise and compare the ovarian tissue immunohistochemical localisation and plasma concentrations of three putative ovarian cancer biomarkers: human cationic antimicrobial protein-18 (hCAP-18); lactoferrin; and CD163 in normal healthy women and women with ovarian cancer.MethodsIn this case–control cohort study, ovarian tissue and blood samples were obtained from 164 women (73 controls, including 28 women with benign pelvic masses; 91 cancer, including 21 women with borderline tumours). Localisation of each antigen within the ovary was assessed by immunohistochemistry and serum concentrations determined by ELISA assays.ResultsImmunoreactive (ir) hCAP-18 and lactoferrin were identified in epithelial cells, while CD163 was predominately localised in stromal cells. Tissue ir CD163 increased significantly (P<0.05) with disease grade. Median plasma concentrations of soluble (s)CD163 were significantly greater in the cases (3220 ng/ml) than in controls (2488 ng/ml) (P< 0.01). Median plasma concentrations of hCAP-18 and lactoferrin were not significantly different between cases and controls. The classification efficiency of each biomarker (as determined by the area under the receiver operator characteristic curve; AUC) was: 0.67± 0.04; 0.62 ± 0.08 and 0.51 ± 0.07 for sCD163, hCAP-18 and lactoferrin, respectively. When the 3 biomarkers were modelled using stochastic gradient boosted logistic regression, the AUC increased to 0.95 ± 0.03.ConclusionsThe data obtained in this study establishes the localisation and concentrations of CD163, hCAP-18, and lactoferrin in ovarian tumours and peripheral blood. Individually, the 3 biomarkers display only modest diagnostic efficiency as assessed by AUC. When combined in a multivariate index assay, however, diagnostic efficiency increases significantly. As such, the utility of the biomarker panel, as an aid in the diagnosis of cancer in symptomatic women, is worthy of further investigation in a larger phase 2 biomarker trial.
Highlights
Epithelial ovarian cancer is one of the leading causes of gynaecological cancer morbidity and mortality in women
When ovarian cancer is identified at an early stage, five year survival increases to ~80%
Study design The experimental design used to evaluate the diagnostic efficiency of plasma concentrations of human cationic antimicrobial protein-18 (hCAP-18), lactoferrin and CD163 was a retrospective case control study
Summary
Epithelial ovarian cancer is one of the leading causes of gynaecological cancer morbidity and mortality in women. More than 200,000 women are diagnosed with ovarian cancer. The average five-year survival rate for ovarian cancer patients is approximately 46%. This high overall mortality is a consequence of a failure to detect this disease at an early stage. When ovarian cancer is identified at an early stage, five year survival increases to ~80%. Recent cohort studies [4,5] highlight the failure of the currently available diagnostic tests to identify ovarian cancer early enough to affect disease progression and outcome. The development of more accurate and earlier detection tests for ovarian cancer in pre-symptomatic women are undoubtedly the number one priority for achieving long-term reduction of mortality from ovarian cancer [3]
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