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Article Open Access

Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer

  • Authors:
    • Karina Dahl Steffensen
    • Marianne Waldstrøm
    • Ivan Brandslund
    • Bente Lund
    • Sarah Mejer Sørensen
    • Max Petzold
    • Anders Jakobsen
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Vejle Hospital, DK‑7100 Vejle, Denmark, Department of Pathology, Vejle Hospital, DK‑7100 Vejle, Denmark, Department of Clinical Biochemistry, Vejle Hospital, DK‑7100 Vejle, Denmark, Department of Oncology, Aalborg University Hospital, DK‑9100 Aalborg, Denmark, Faculty of Health Sciences, University of Copenhagen, DK‑2200 Copenhagen, Denmark, Centre for Applied Biostatistics, Sahlgrenska Academy, University of Gothenburg, S‑405 30 Gothenburg, Sweden
    Copyright: © Steffensen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3967-3974
    |
    Published online on: May 6, 2016
       https://doi.org/10.3892/ol.2016.4533
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Abstract

The majority of ovarian cancer patients with advanced disease at diagnosis will relapse following primary treatment, with a dismal prognosis. Monitoring the levels of serum markers in patients under follow‑up may be essential for the early detection of relapse, and for distinguishing high‑risk patients from those with less aggressive disease. The aim of the present study was to investigate the possible predictive value of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in relation to recurrence of epithelial ovarian cancer by measuring the two markers during follow‑up subsequent to surgery and adjuvant first‑line carboplatin/paclitaxel chemotherapy. Serum HE4 and CA125 were analyzed in 88 epithelial ovarian cancer patients at the end of treatment and consecutively during follow‑up. The patients were divided into a high‑risk and a low‑risk group based on having an increase in HE4 and CA125 levels above or below 50% during follow‑up, relative to the baseline (end‑of‑treatment) level. Disease recurrence was detected in 55 patients during follow‑up. Patients with an increase in HE4 of >50% at 3‑ and 6‑month follow‑up compared to the end‑of‑treatment sample had significantly poorer progression‑free survival (PFS) [hazard ratio (HR), 2.82 (95% CI, 0.91‑8.79; P=0.0052) and HR, 7.71 (95% CI, 3.03‑19.58; P<0.0001), respectively]. The corresponding 3‑ and 6‑month biomarker assessments for increased CA125 levels (>50%) showed HRs of 1.86 (95% CI, 0.90‑3.80; P=0.0512) and 2.55 (95% CI, 1.39‑4.68; P=0.0011), respectively. Multivariate analysis confirmed HE4 as a predictor of short PFS, with an HR of 8.23 (95% CI, 3.28‑20.9; P<0.0001) at 6‑month follow‑up. The increase of CA125 was not a significant prognostic factor in multivariate analysis for PFS. In conclusion, HE4 appears to be a sensitive marker of recurrence and instrumental in risk assessment during the first 6 months of follow‑up.
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1 

Siegel R, Naishadham MA and Jemal A: Cancer statistics 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Liu PY, Alberts DS, Monk BJ, Brady M, Moon J and Markman M: An early signal of CA-125 progression for ovarian cancer patients receiving maintenance treatment after complete clinical response to primary therapy. J Clin Oncol. 25:3615–3620. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Vergote I, Rustin GJ, Eisenhauer EA, Kristensen GB, Pujade-Lauraine E, Parmar MK, Friedlander M, Jakobsen A and Vermorken JB: Re: New guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]. Gynecologic Cancer Intergroup. J Natl Cancer Inst. 92:1534–1535. 2000. View Article : Google Scholar : PubMed/NCBI

4 

Rustin GJ, Nelstrop AE, Tuxen MK and Lambert HE: Defining progression of ovarian carcinoma during follow-up according to CA 125: A north thames ovary group study. Ann Oncol. 7:361–364. 1996. View Article : Google Scholar : PubMed/NCBI

5 

Tuxen MK, Sölétormos G and Dombernowsky P: Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up. Scand J Clin Lab Invest. 62:177–188. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Rustin GJ, van der Burg ME, Griffin CL, Guthrie D, Lamont A, Jayson GC, Kristensen G, Mediola C, Coens C, Qian W, et al: Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): A randomised trial. Lancet. 376:1155–1163. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Harter P: DESKTOP III (AGO-OVAR OP.4): A randomized trial evaluating cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer. http://www.gcig.igcs.org/ClinicalTrials.html

8 

Fleming ND, Cass I, Walsh CS, Karlan BY and Li AJ: CA125 surveillance increases optimal resectability at secondary cytoreductive surgery for recurrent epithelial ovarian cancer. Gynecol Oncol. 121:249–252. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Einhorn N, Bast RC Jr, Knapp RC, Tjernberg B and Zurawski VR Jr: Preoperative evaluation of serum CA 125 levels in patients with primary epithelial ovarian cancer. Obstet Gynecol. 67:414–416. 1986.PubMed/NCBI

10 

Clauss A, Lilja H and Lundwall A: A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein. Biochem J. 368:233–242. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Bouchard D, Morisset D, Bourbonnais Y and Tremblay GM: Proteins with whey-acidic-protein motifs and cancer. Lancet Oncol. 7:167–174. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Bouchard D, Morisset D, Bourbonnais Y and Tremblay GM: Proteins with whey-acidic-protein motifs and cancer. Lancet Oncol. 7:167–174. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Galgano MT, Hampton GM and Frierson HF Jr: Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol. 19:847–853. 2006.PubMed/NCBI

14 

Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR and Hecht JL: Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 65:2162–2169. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Hellström I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, Drescher C, Urban N and Hellström KE: The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 63:3695–3700. 2003.PubMed/NCBI

16 

Hellstrom I and Hellstrom 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. 622:15–21. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Hellstrom I and Hellstrom KE: fTwo novel biomarkers, mesothelin and HE4, for diagnosis of ovarian carcinoma. Expert Opin Med Diagn. 5:227–240. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Montagnana M, Lippi G, Ruzzenente O, Bresciani V, Danese E, Scevarolli S, Salvagno GL, Giudici S, Franchi M and Guidi GC: The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass. J Clin Lab Anal. 23:331–335. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, Steinhoff M, Messerlian G, DiSilvestro P, Granai CO and Bast RC Jr: The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 108:402–408. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, Gajewski W, Kurman R, Bast RC Jr and Skates SJ: A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol. 112:40–46. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Steffensen KD, Waldstrøm M, Brandslund I and Jakobsen A: Prognostic impact of prechemotherapy serum levels of HER2, CA125, and HE4 in ovarian cancer patients. Int J Gynecol Cancer. 21:1040–1047. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Steffensen KD, Waldstrøm M and Jakobsen A: The relationship of platinum resistance and ERCC1 protein expression in epithelial ovarian cancer. Int J Gynecol Cancer. 19:820–825. 2009. View Article : Google Scholar : PubMed/NCBI

23 

World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 310:2191–2194. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Rustin GJ: Use of CA-125 to assess response to new agents in ovarian cancer trials. J Clin Oncol. 21(Suppl 10): S187–S193. 2003. View Article : Google Scholar

25 

Rustin GJ, Quinn M, Thigpen T, du Bois A, Pujade-Lauraine E, Jakobsen A, Eisenhauer E, Sagae S, Greven K, Vergote I, et al: Re: New guidelines to evaluate the response to treatment in solid tumors (ovarian cancer). J Natl Cancer Inst. 96:487–488. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Havrilesky LJ, Whitehead CM, Rubatt JM, Cheek RL, Groelke J, He Q, Malinowski DP, Fischer TJ and Berchuck A: Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol. 110:374–382. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Plotti F, Capriglione S, Terranova C, Montera R, Aloisi A, Damiani P, Muzii L, Scaletta G, Benedetti-Panici P and Angioli R: Does HE4 have a role as biomarker in the recurrence of ovarian cancer? Tumour Biol. 33:2117–2123. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Manganaro L, Michienzi S, Vinci V, Falzarano R, Saldari M, Granato T, Viggiani V, Frati L and Anastasi E: Serum HE4 levels combined with CE CT imaging improve the management of monitoring women affected by epithelial ovarian cancer. Oncol Rep. 30:2481–2487. 2013.PubMed/NCBI

29 

Anastasi E, Marchei GG, Viggiani V, Gennarini G, Frati L and Reale MG: HE4: A new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol. 31:113–119. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Schummer M, Drescher C, Forrest R, Gough S, Thorpe J, Hellström I, Hellström KE and Urban N: Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125. Gynecol Oncol. 125:65–69. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Granato T, Midulla C, Longo F, Colaprisca B, Frati L and Anastasi E: Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer. Tumour Biol. 33:1335–1339. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Steffensen KD, Waldstrøm M, Brandslund I, Petzold M and Jakobsen A: The prognostic and predictive value of combined HE4 and CA-125 in ovarian cancer patients. Int J Gynecol Cancer. 22:1474–1482. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Rustin GJ, van der Burg ME, Griffin CL, Guthrie D, Lamont A, Jayson GC, Kristensen G, Mediola C, Coens C, Qian W, et al: Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): A randomised trial. Lancet. 376:1155–1163. 2010. View Article : Google Scholar : PubMed/NCBI

34 

National Cancer Institute: Cancer statistics: SEER stat fact sheets, ovary cancer. http://seer.cancer.gov/statfacts/html/ovary.htmlAccessed. April 14–2016

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Copy and paste a formatted citation
Spandidos Publications style
Steffensen KD, Waldstrøm M, Brandslund I, Lund B, Sørensen SM, Petzold M and Jakobsen A: Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer. Oncol Lett 11: 3967-3974, 2016.
APA
Steffensen, K.D., Waldstrøm, M., Brandslund, I., Lund, B., Sørensen, S.M., Petzold, M., & Jakobsen, A. (2016). Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer. Oncology Letters, 11, 3967-3974. https://doi.org/10.3892/ol.2016.4533
MLA
Steffensen, K. D., Waldstrøm, M., Brandslund, I., Lund, B., Sørensen, S. M., Petzold, M., Jakobsen, A."Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer". Oncology Letters 11.6 (2016): 3967-3974.
Chicago
Steffensen, K. D., Waldstrøm, M., Brandslund, I., Lund, B., Sørensen, S. M., Petzold, M., Jakobsen, A."Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer". Oncology Letters 11, no. 6 (2016): 3967-3974. https://doi.org/10.3892/ol.2016.4533
Copy and paste a formatted citation
x
Spandidos Publications style
Steffensen KD, Waldstrøm M, Brandslund I, Lund B, Sørensen SM, Petzold M and Jakobsen A: Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer. Oncol Lett 11: 3967-3974, 2016.
APA
Steffensen, K.D., Waldstrøm, M., Brandslund, I., Lund, B., Sørensen, S.M., Petzold, M., & Jakobsen, A. (2016). Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer. Oncology Letters, 11, 3967-3974. https://doi.org/10.3892/ol.2016.4533
MLA
Steffensen, K. D., Waldstrøm, M., Brandslund, I., Lund, B., Sørensen, S. M., Petzold, M., Jakobsen, A."Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer". Oncology Letters 11.6 (2016): 3967-3974.
Chicago
Steffensen, K. D., Waldstrøm, M., Brandslund, I., Lund, B., Sørensen, S. M., Petzold, M., Jakobsen, A."Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer". Oncology Letters 11, no. 6 (2016): 3967-3974. https://doi.org/10.3892/ol.2016.4533
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