Soluble Epidermal Growth Factor Receptor (sEGFR/sErbB1) as a Potential Risk, Screening, and Diagnostic Serum Biomarker of Epithelial Ovarian Cancer

Soluble Epidermal Growth Factor Receptor (sEGFR/sErbB1) as a Potential Risk, Screening, and Diagnostic Serum Biomarker of Epithelial Ovarian Cancer1

Tumor Biology Program [A. T. B., J. M. L., N. J. M.], Department of Gynecologic Surgery/Oncology [K. C. P.], and Department of Family Medicine [M. C. B.], Mayo Clinic-Rochester, Rochester, Minnesota 55905; Department of Biochemistry and Nutrition, University of Puerto Rico, Medical Sciences Campus, School of Medicine, San Juan, Puerto Rico 00936-5067 [E. M. C.]; Departments of Preventive Medicine [A. R., D. L.] and Obstetrics and Gynecology [D. A. F.], Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611; and Department of Obstetrics and Gynecology, Medical College of Virginia, Virginia Commonwealth University Health System, Richmond, Virginia 23298-0034 [C. H. B.]

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies in the United States, for which risk assessment, screening, and diagnostic tests are needed. We have shown previously that women with stage III/IV EOC have lower serum p110 sEGFR/sErbB1 (Soluble Epidermal Growth Factor Receptor) concentrations than healthy women. Here, we show that serum p110 sEGFR/sErbB1 is the product of a 3-kb EGFR/ERBB1 alternate transcript. We report that serum sEGFR concentrations in stage I/II and stage III/IV EOC patients are significantly lower than in healthy women, and that serum sEGFR concentrations are not associated with disease stage or tumor grade. Logistic regression models show that: (a) lower serum sEGFR concentrations are associated significantly with a greater risk of EOC; (b) the risk associated with lower serum sEGFR concentrations is reduced by older age or menopause; and (c) age- or menopausal status-specific cutoff values for sEGFR concentration are appropriate. Receiver operating characteristic curves indicate that: (a) serum sEGFR concentrations are more effective in discerning stage III/IV than stage I/II EOC cases from healthy women; and (b) sEGFR concentrations have an 89% probability of correctly discerning EOC patients from healthy women when accounting for effect modification by age. By maintaining a test specificity of ∼95% across strata of age or menopausal status with appropriate cutoff values, we observe that sEGFR concentrations are most useful for detecting stage I/II (sensitivity: 64–67%) and stage III/IV (sensitivity: 75–81%) EOC in young, premenopausal women. We conclude that serum sEGFR concentrations warrant additional investigation in the risk assessment, early detection, and/or diagnosis of EOC.

Footnotes

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↵1 This work was supported by NIH Grants KO7 CA76170, R21 CA82520, and RO3 CA82091 (to A. T. B.); KO1 CA73859 (to E. M. C.); RO1 57534 and UO1 CA85133 (to N. J. M. and D. A. F.); and by the NIH Office of Women’s Health Research and National Ovarian Cancer Early Detection Research Network, sponsored by the National Cancer Institute.
↵2 These authors contributed equally to this work.
↵3 To whom requests for reprints should be addressed, at Tumor Biology Program, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Phone: (507) 284-0279; Fax: (507) 284-1767; E-mail: Maihle.Nita{at}Mayo.edu
↵4 The abbreviations used are: EOC, epithelial ovarian cancer; EGFR, epidermal growth factor receptor; sErbB, soluble ErbB; ALISA, acridinium-linked immunosorbent assay; MAb, monoclonal antibody; NCI, National Cancer Institute; GOG, Gynecologic Oncology Group; ALBB, acridinium-linked immunosorbent assay blocking buffer; RLU, relative light unit; ROC, receiver operating characteristic; AUC, area under the curve; CI, confidence interval; OR, odds ratio; BDL, biological detection limit; SD, standard deviation.
- Accepted December 4, 1902.
- Received July 15, 1902.
- Revision received November 8, 1902.