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Ovarian tumor marker HE4 is differently expressed during the phases of the menstrual cycle in healthy young women

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Tumor Biology

Abstract

The objective of the present study was to investigate in healthy young women the fluctuations in serum concentration of human epididymal secretory protein human epididymis-specific protein 4 (HE4) and CA125 during the phases of the menstrual cycle and the correlation between HE4 and CA125 values and age. Forty women with regular menstrual cycles were included in the study. Pelvic and transvaginal ultrasound were performed in order to exclude ovarian pathologies. Blood samples were collected at follicular (FP), ovulatory (OP), and luteal (LP) phases of the hormonal cycle. The values of HE4 (expressed as picomoles per liter) observed were (mean ± SEM) 39.1 ± 1.1 (FP), 45.3 ± 1.19 (OP), and 42.0 ± 1.3 (LP). The difference between FP and OP was statistically significant (p = 0.0002). By contrast, serum CA125 levels (expressed as units per milliliter) were 14.35 ± 0.66 (FP), 13.15 ± 0.54 (OP), and 13.70 ± 0.54 (LP), respectively. The levels of HE4 observed in serum samples of women below 35 years were 37.5 ± 1.28 in the FP, 46.6 ± 1.4 in the OP, and 42.8 ± 1.49 in the LP. In this group, a statistically significant difference was observed in the FP compared with the OP (p < 0.0001), whereas no statistically significant difference was observed during the different hormonal phases in the group of women over 35. In conclusion, the correct interpretation of laboratory data is essential to define a threshold of normality, and for what concerns HE4 levels, the menstrual cycle phase-dependent variability appears indicated in the interpretation of the results.

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References

  1. Mallett S, Timmer A, Sauerbrei W, Altaman DG. Reporting of prognostic studies of tumor markers: a review of articles in relation to REMARK guidelines. Br J Cancer. 2010;102:173–80.

    Article  CAS  PubMed  Google Scholar 

  2. Meany DL, Sokoll LJ, Chan DW. Early detection of cancer: immunoassay for plasma tumor markers. Expert Opin Med Diagn. 2009;3:597–605.

    Article  CAS  PubMed  Google Scholar 

  3. Glassman RH, Ratain MJ. Biomarkers in early cancer drug development: limited utility. Pharmacol Ther. 2009;85:134–5.

    Article  CAS  Google Scholar 

  4. Simon R. Clinical trial for evaluating the medical utility of prognostic and predictive biomarkers in oncology. Per Med. 2010;7:33–47.

    Article  PubMed  Google Scholar 

  5. Bon GS, Kenemans P, Dekker JJ, Hompes PG, Verstraeten RA, van Kamp GJ, et al. Fluctuations in CA125 and Ca15-3 serum concentrations during spontaneous ovulatory cycles. Hum Reprod. 1999;14:566–70.

    Article  CAS  PubMed  Google Scholar 

  6. Kafali H, Artunc H, Herdem M. Evaluation of factors that may be responsible for cyclic change of CA125 levels during menstrual cycle. Arch Gynecol Obstet. 2007;275:175–7.

    Article  CAS  PubMed  Google Scholar 

  7. Kirchhoff C. Molecular characterization of epididymal proteins. Rev Reprod. 1998;3:86–95.

    Article  CAS  PubMed  Google Scholar 

  8. Bingle L, Singleton V, Bingle CD. The putative ovarian tumor marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein is forms. Ontogeny. 2002;21:2768–73.

    CAS  Google Scholar 

  9. Claus A, Lila H, Lund wall A. The evolution of a genetic locus encoding small serine proteins inhibitors. Brioche Biophysics Res Common. 2005;333:383–9.

    Article  Google Scholar 

  10. Claus A, Lila H, Lund wall A. A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acid protein. Brioche J. 2002;368:233–42.

    Google Scholar 

  11. Hellerstrom I, Hellertown KE. SMRP and HE4 as biomarkers for ovarian carcinoma when used alone and in combination with CA125 and/or each other. Adv Exp Med Biol. 2008;622:15–21.

    Article  Google Scholar 

  12. Anastasi E, Marchei GG, Viggiani V, Gennarini G, Frati L, Reale MG. HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumor Biol. 2010;31:113–9.

    Article  CAS  Google Scholar 

  13. Chen DX, Schwartz PE, Li XG, Yang Z. Evaluation of CA125 levels in differentiating malignant from benign tumors in patients with pelvic mass. Obstet Gynecol. 1988;72:23–7.

    CAS  PubMed  Google Scholar 

  14. Medeiros LR, Rosa DD, da Rosa MI, Bozzetti MC. Accuracy of CA125 in the diagnosis of ovarian tumors: a quantitative systematic review. Eur J Obstet Gynecol Reprod Biol. 2009;142:99–105.

    CAS  PubMed  Google Scholar 

  15. Tian C, Markman M, Zaino R, Ozols RF, McGuire WP, Muggia FM, et al. CA125 change after chemotherapy in prediction of treatment outcome among advanced mucinous and clear cell epithelial ovarian cancers: a Gynecologic Oncology Group study. Cancer. 2009;115:1395–403.

    Article  CAS  PubMed  Google Scholar 

  16. Urban N, McIntosh AM, Karlan B. Ovarian cancer screening. Hematol Oncol Clin North Am. 2003;17:989–1005.

    Article  PubMed  Google Scholar 

  17. Ozols RF. Recurrent ovarian cancer: evidence-based treatment. J Clin Oncol. 2002;20:1161–3.

    PubMed  Google Scholar 

  18. Boffetta P. Biomarkers in cancer epidemiology an integrative approach. Carcinogenesis. 2009;31:121–6.

    Article  PubMed  Google Scholar 

  19. Riley RD, Saurbrei W, Altman DG. Prognostic markers in cancer: the evolution of evidence from single studies to meta-analysis and beyond. Br J Cancer. 2009;100:1219–29.

    Article  CAS  PubMed  Google Scholar 

  20. Planchard D, Loriot Y, Goubar A, Commo SJC. Differential expression of biomarkers in men and women. Semin Oncol. 2009;36:553–65.

    Article  CAS  PubMed  Google Scholar 

  21. Kafali H, Artuc H, Demir N. Use of CA125 fluctuation during the menstrual cycle as a tool in the clinical diagnosis of endometriosis; a preliminary study. Eur J Obstet Gynecol Reprod Bio. 2004;116:85–8.

    Article  CAS  Google Scholar 

  22. Erbagci AB, Ylmaz N, Kutlar I. Menstrual cycle dependent variability for serum tumor markers CEA, AFP, CA 19-9, CA125 and CA15-3 in healthy women. Dis Markers. 1999;15:259–67.

    CAS  PubMed  Google Scholar 

  23. Zweers A, de Boever J, Serreyn R, Vandekerckhove D. Correlation between peripheral CA125 and ovarian activity. Fertil Steril. 1990;54:490–4.

    Google Scholar 

  24. Kafali H, Artunc H, Erdem M. Evaluation of factors that may be responsible for cyclic change of CA125 levels during menstrual cycle. Arch Gynecol Obstet. 2007;275:175–7.

    Article  CAS  PubMed  Google Scholar 

  25. Creaney J, Robinson BW. Serum and pleural fluid biomarkers for mesothelioma. Curr Opin Pulm Med. 2009;15:366–70.

    Article  CAS  PubMed  Google Scholar 

  26. Zeimet AG, Muller-Holzner E, Marth C, Daxenbichler G, Dapunt O. Tumor marker CA125 in tissues of the female reproductive tract and in serum during the normal menstrual cycle. Fertil Steril. 1993;59:1028–35.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This study is founded by the University of Rome “Sapienza”. We are thankful to Giuseppina Gennarini and Silvestra Tudini for their technical assistance.

Conflict of interest statement

None declared.

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Authors and Affiliations

  1. Department of Oncology, University “Sapienza”, 00161, Rome, Italy

    Emanuela Anastasi, Giulia Giovanna Marchei, Valentina Viggiani, Barbara Colaprisca, Sara Comploj, Maria Gabriella Reale, Luigi Frati & Cecilia Midulla

  2. CNR IBPM, Consiglio Nazionale Ricerche, Rome, Italy

    Teresa Granato

  3. Laboratory of Tumor Markers, Department of Oncology, University “Sapienza”, Viale Regina Elena 324, 00161, Rome, Italy

    Emanuela Anastasi

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  1. Emanuela Anastasi
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  2. Teresa Granato
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  3. Giulia Giovanna Marchei
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  4. Valentina Viggiani
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  5. Barbara Colaprisca
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  6. Sara Comploj
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  7. Maria Gabriella Reale
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  8. Luigi Frati
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  9. Cecilia Midulla
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Correspondence to Emanuela Anastasi.

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Anastasi, E., Granato, T., Marchei, G.G. et al. Ovarian tumor marker HE4 is differently expressed during the phases of the menstrual cycle in healthy young women. Tumor Biol. 31, 411–415 (2010). https://doi.org/10.1007/s13277-010-0049-1

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  • DOI: https://doi.org/10.1007/s13277-010-0049-1

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