Soluble Epidermal Growth Factor Receptor (SEG-FR) and Cancer Antigen 125 (CA125) as Screening and Diagnostic Tests for Epithelial Ovarian Cancer

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecologic cancers in the United States. Because women who are diagnosed with early stage disease have a better prognosis than women diagnosed with late stage disease, early detection represents a potentially practical approach to reduce the mortality associated with EOC. Unfortunately, no single screening test has proven to be effective for this purpose, and a valid and feasible screening program to detect early stage EOC in the general population has not yet been devised. Consequently, research has focused on coupling two or more screening modalities to improve program validity and feasibility. Serum cancer antigen 125 (CA125) and a soluble isoform of the epidermal growth factor receptor (p110 sEGFR) have been studied individually as biomarkers of ovarian cancer. In this study, we compare serum CA125 levels and sEGFR concentrations in women with EOC to women with benign gynecologic conditions of ovarian and non-ovarian origin. We show that serum sEGFR concentrations are lower in patients with EOC than in women with benign gynecologic conditions, whereas serum CA125 levels are higher in patients to EOC compared with women with benign gynecologic conditions. These data also reveal that age and serum sEGFR concentrations modify the association between CA125 levels and EOC versus benign gynecologic disease. Hence, age-and sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern EOC patients from women with benign ovarian tumors and non-ovarian gynecologic conditions. Our analyses show that parallel testing with fixed sEGFR and CA125 cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing with age-and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity, and overall accuracy to discern patients with EOC from women with benign ovarian and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and CA125, thus, has improved utility for screening and diagnosing EOC, which may increase the positive predictive value of a multimodal screening program that incorporates these biomarkers to detect and subsequently differentiate benign from malignant ovarian tumors. (Cancer Epidemiol Biomarkers Prev 2005;14(2):306 -18)

A Novel Approach to Predict the Likelihood of Specific Ovarian Tumor Pathology Based on Serum CA-125: A Multicenter Observational Study

“…Our results confirm those of previous studies showing that CA-125 levels are higher in premenopausal patients than in postmenopausal patients presenting with a benign tumor but that the opposite is true of patients with a malignant tumor (9,12,33). This can be partly explained by differences in prevalence of endometriomas and advanced ovarian cancers.…”

Identification of salt-inducible kinase 3 as a novel tumor antigen associated with tumorigenesis of ovarian cancer

“…Its soluble proteolytic fragment can be released into the blood stream. Thus, serum CA125 has been studied intensively as a potential biomarker for diagnosis of epithelial ovarian cancer or to monitor disease recurrence after therapy (Baron et al, 2005;Rosenthal et al, 2006). However, elevated CA125 expressions are not only observed in >80% of patients with advanced epithelial ovarian cancer, but are also found in various physiological or pathological conditions (Cannistra, 2004).…”

The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

“…[1] Although a single determination of CA-125 does not have the sensitivity, specificity and positive predictive value to be used as a stand-alone screen, CA-125 measurement may be shown to be a valuable part of a multi-modal and/or longitudinal screening algorithm. [2][3][4][5][6][7][8] If this approach proves feasible, knowledge of the usual pattern of CA-125 levels among populations of women without ovarian cancer will be a prerequisite. [9] CA-125 is an antigenic determinant on a high molecular weight glycoprotein encoded by the MUC16 gene, [10;11] that was first recognized by a monoclonal antibody, OC125, and subsequently a series of other antibodies.…”