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Combined use of biomarkers for detection of ovarian cancer in high-risk women

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Tumor Biology

Abstract

The aim of this study was to examine the negative predictive value for a panel of serum markers in women at high risk for developing ovarian cancer. A total of 201 serum samples were collected and analyzed from 102 women at “high risk” for ovarian cancer: 26 with primary ovarian cancer, 31 with recurrent ovarian cancer, 28 with benign gynecologic diseases, and 14 with other cancers. Samples were tested for cancer antigen (CA) 125 II, CA19-9, CA72-4, CA15-3, and macrophage colony-stimulating factor, OVX1, and the marker values were further used as input to be evaluated by a previously trained artificial neural network (ANN). CA125 alone identified 72% of the primary ovarian cancers at a specificity of 95%. If either CA125 or CA72-4 were elevated, sensitivity rose to 80%. Adding macrophage colony-stimulating factor–improved sensitivity to 84% and when CA15-3 was included, a sensitivity of 88% was achieved. Specificity of the four marker panel was, however, reduced to 82.5%. By contrast, at the same sensitivity of 88%, the ANN exhibited a much higher specificity at 92.5% (p = 0.0105). Our data suggest that the combined use of multiple biomarkers improve sensitivity in women at high risk for ovarian cancer. In contrast to the simple “or” combination rule, the ANN was able to achieve a higher sensitivity without significant loss in specificity.

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References

  1. Bast Jr RC, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983;309:883–7.

    Article  PubMed  Google Scholar 

  2. Zanaboni F, Vergadoro F, Presti M, Gallotti P, Lombardi F, Bolis G. Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma. Gynecol Oncol. 1987;28:61–7.

    Article  CAS  PubMed  Google Scholar 

  3. Zurawski Jr VR, Orjaseter H, Andersen A, Jellum E. Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: relevance for early detection of ovarian cancer. Int J Cancer. 1988;42:677–80.

    Article  PubMed  Google Scholar 

  4. Zurawski Jr VR, Knapp RC, Einhorn N, Kenemans P, Mortel R, Ohmi K, et al. An initial analysis of preoperative serum CA 125 levels in patients with early stage ovarian carcinoma. Gynecol Oncol. 1988;30:7–14.

    Article  PubMed  Google Scholar 

  5. Malkasian Jr GD, Knapp RC, Lavin PT, Zurawski Jr VR, Podratz KC, Stanhope CR, et al. Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses: discrimination of benign from malignant disease. Am J Obstet Gynecol. 1988;159:341–6.

    PubMed  Google Scholar 

  6. Patsner B, Mann WJ. The value of preoperative serum CA 125 levels in patients with a pelvic mass. Am J Obstet Gynecol. 1988;159:873–6.

    CAS  PubMed  Google Scholar 

  7. Vasilev SA, Schlaerth JB, Campeau J, Morrow CP. Serum CA 125 levels in preoperative evaluation of pelvic masses. Obstet Gynecol. 1988;71:751–6.

    CAS  PubMed  Google Scholar 

  8. Gadducci A, Ferdeghini M, Prontera C, Moretti L, Mariani G, Bianchi R, et al. The concomitant determination of different tumor markers in patients with epithelial ovarian cancer and benign ovarian masses: relevance for differential diagnosis. Gynecol Oncol. 1992;44:147–54.

    Article  CAS  PubMed  Google Scholar 

  9. Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351:2519–29.

    Article  CAS  PubMed  Google Scholar 

  10. Bast Jr RC, Badgwell D, Lu Z, Marquez R, Rosen D, Liu J, et al. New tumor markers: CA125 and beyond. Int J Gynecol Cancer. 2005;3:274–81.

    Article  Google Scholar 

  11. Zhang Z, Barnhill SD, Zhang H, Xu F, Yu Y, Jacobs I, et al. Combination of multiple serum markers using an artificial neural network to improve specificity in discriminating malignant from benign pelvic masses. Gynecol Oncol. 1999;73:56–61.

    Article  CAS  PubMed  Google Scholar 

  12. Lawicki S, Szmitkowski M, Wojtukiewicz M. The pretreatment plasma level and diagnostic utility of M-CSF in benign breast tumor and breast cancer patients. Clin Chim Acta. 2006;371:112–6.

    Article  CAS  PubMed  Google Scholar 

  13. Trecate G, Vergnaghi D, Manoukian S, Bergonzi S, Scaperrotta G, Marchesini M, et al. MRI in the early detection of breast cancer in women with high genetic risk. Tumori. 2006;92:517–23.

    PubMed  Google Scholar 

  14. Olivier RI, Lubsen-Brandsma MA, Verhoef S, van Beurden M. CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol Oncol. 2006;100:20–6.

    Article  CAS  PubMed  Google Scholar 

  15. Woolas RP, Xu FJ, Jacobs IJ, Yu YH, Daly L, Berchuck A, et al. Elevation of multiple serum markers in patients with stage I ovarian cancer. J Natl Cancer Inst. 1993;85:1748–51.

    Article  CAS  PubMed  Google Scholar 

  16. Xu FJ, Yu YH, Li BY, Moradi M, Elg S, Lane C, et al. Development of two new monoclonal antibodies reactive to a surface antigen present on human ovarian epithelial cancer cells. Cancer Res. 1991;51:4012–9.

    CAS  PubMed  Google Scholar 

  17. Xu FJ, Ramakrishnan S, Daly L, Soper JT, Berchuck A, Clarke-Pearson D, et al. Increased serum levels of macrophage colony-stimulating factor in ovarian cancer. Am J Obstet Gynecol. 1991;165:1356–62.

    CAS  PubMed  Google Scholar 

  18. Skates SJ, Horick N, Yu Y, Xu FJ, Berchuck A, Havrilesky LJ, et al. Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions. J Clin Oncol. 2004;22:4059–66.

    Article  PubMed  Google Scholar 

  19. Zhang Z, Yu Y, Xu F, Berchuck A, van Haaften-Day C, Havrilesky LJ, et al. Combining multiple serum tumor markers improves detection of stage I epithelial ovarian cancer. Gynecol Oncol. 2007;107:526–31.

    Article  CAS  PubMed  Google Scholar 

  20. Park BW, Oh JW, Kim JH, Park SH, Kim KS, Kim JH, et al. Preoperative CA 15-3 and CEA serum levels as predictor for breast cancer outcomes. Ann Oncol. 2008;19:675–81.

    Article  PubMed  Google Scholar 

  21. Joyner AB, Runowicz CD. Ovarian cancer screening and early detection. Womens Health (Lond Engl). 2009;5:693–9. Review.

    Google Scholar 

  22. van Haaften-Day C, Shen Y, Xu F, Yu Y, Berchuck A, Havrilesky LJ, et al. OVX1, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma: a critical appraisal. Cancer. 2001;92:2837–44.

    Article  PubMed  Google Scholar 

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Acknowledgements

Thanks to Fujirebio Diagnostics Inc for providing Radioimmunoassay kits of CA125II, CA72-4, CA15-3, and CA19-9.

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Author notes

  1. Yinhua Yu & Weiwei Feng

    Present address: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China

Authors and Affiliations

  1. Istituto Oncologico Veneto IRCCS, Padua, Italy

    Martin Donach, Grazia Artioli, Giuseppe Banna & Maria O. Nicoletto

  2. M.D. Anderson Cancer, The University of Texas, Houston, TX, USA

    Yinhua Yu, Weiwei Feng & Robert C. Bast Jr.

  3. Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Zhen Zhang

  4. Center for Biomarker Discovery, Johns Hopkins Medical Institutions, CRB-II 3M04, 1550 Orleans Street, Baltimore, MD, 21231, USA

    Zhen Zhang

  5. Medical Oncology, Istituto Oncologico Veneto IRCCS, Ospedale Busonera, 1st floor, Via Gattamelata 64, 35128, Padua, Italy

    Maria O. Nicoletto

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  1. Martin Donach
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  2. Yinhua Yu
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  3. Grazia Artioli
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  5. Weiwei Feng
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  6. Robert C. Bast Jr.
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  7. Zhen Zhang
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  8. Maria O. Nicoletto
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Correspondence to Zhen Zhang or Maria O. Nicoletto.

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Donach, M., Yu, Y., Artioli, G. et al. Combined use of biomarkers for detection of ovarian cancer in high-risk women. Tumor Biol. 31, 209–215 (2010). https://doi.org/10.1007/s13277-010-0032-x

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  • DOI: https://doi.org/10.1007/s13277-010-0032-x

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