Skip to main content
Top
Published in: Tumor Biology 5/2013

01-10-2013 | Research Article

The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients

Authors: Beyhan Omer, Sema Genc, Ozguc Takmaz, Ahmet Dirican, Zeynep Kusku-Kiraz, Sinan Berkman, Figen Gurdol

Published in: Tumor Biology | Issue 5/2013

Login to get access

Abstract

The aim of this study was to evaluate the prognostic and predictive efficacy of the human epididymis secretory protein 4 (HE4) and serum amyloid-A (S-AA) together with the other tumor markers (CA 125, CA 15–3, CEA, and CA 19–9) in endometrial cancer patients. The study group consisted of 64 patients with defined stage and grade of endometrial cancer and 60 women with benign uterine diseases. Thirty-four healthy women were defined as the control group. Fasting blood samples were collected prior to surgery and tumor marker levels were determined in blood samples by E170 autoanalyzer. S-AA concentrations were measured by particle-enhanced immunonephelometry. Preoperative serum HE4 and S-AA levels were significantly higher in endometrial cancer patients than in controls, whereas the other measured parameters were not significantly different. Serum levels of HE4 were related to both the stage and grade of tumor. The best cutoff point for HE4 was determined to be 59.7 pmol/L; with 75 % sensitivity and 65.5 % specificity. For S-AA, the cutoff point was 8.8 U/mL, with 68.7 % sensitivity and 58.6 % specificity. The combination of HE4, CA 125, CEA, and S-AA raised the sensitivity to 84 %. Preoperative measurement of serum HE4 and S-AA may be of help in early detection of endometrial cancer. Preoperative screening with these markers may provide important information about the patient’s outcome and prognosis.
Literature
2.
go back to reference Sohaib SA, Houghton SL, Meroni R, et al. Recurrent endometrial cancer: patterns of recurrent disease and assessment of prognosis. Clin Radiol. 2007;62:28–34.CrossRefPubMed Sohaib SA, Houghton SL, Meroni R, et al. Recurrent endometrial cancer: patterns of recurrent disease and assessment of prognosis. Clin Radiol. 2007;62:28–34.CrossRefPubMed
3.
go back to reference Rose SL, Bradley SL, Lutgendorf SK, Sorosky J, Anderson B. The impact of adjuvant radiation therapy on long-term quality of life in patients with stage I endometrial cancer. Gynecol Oncol. 2004;92:479–80. Rose SL, Bradley SL, Lutgendorf SK, Sorosky J, Anderson B. The impact of adjuvant radiation therapy on long-term quality of life in patients with stage I endometrial cancer. Gynecol Oncol. 2004;92:479–80.
5.
go back to reference Taioli E, Kinney P, Zhitkovich A, et al. Application of reliability models to studies of biomarker validation. Environ Health Perspect. 1994;102:306–9.PubMedCentralCrossRefPubMed Taioli E, Kinney P, Zhitkovich A, et al. Application of reliability models to studies of biomarker validation. Environ Health Perspect. 1994;102:306–9.PubMedCentralCrossRefPubMed
6.
go back to reference Arslan AA, Zeleniuch-Jacquotte A, Lukanova A, et al. Reliability of follicle-stimulating hormone measurements in serum. Reprod Biol Endocrinol. 2003;1:49.PubMedCentralCrossRefPubMed Arslan AA, Zeleniuch-Jacquotte A, Lukanova A, et al. Reliability of follicle-stimulating hormone measurements in serum. Reprod Biol Endocrinol. 2003;1:49.PubMedCentralCrossRefPubMed
7.
go back to reference Touitou Y, Bogdan A. Tumor markers in non-malignant diseases. Eur J Cancer Clin Oncol. 1988;24:1083–91.CrossRefPubMed Touitou Y, Bogdan A. Tumor markers in non-malignant diseases. Eur J Cancer Clin Oncol. 1988;24:1083–91.CrossRefPubMed
8.
go back to reference Gadducci A, Ferfeghini M, Prontera C, et al. A comparison of pretreatment serum levels of four tumor markers in patients with endometrial and cervical cancer. Eur J Gynaecol Oncol. 1990;1:283–8. Gadducci A, Ferfeghini M, Prontera C, et al. A comparison of pretreatment serum levels of four tumor markers in patients with endometrial and cervical cancer. Eur J Gynaecol Oncol. 1990;1:283–8.
9.
go back to reference Hsieh CH, ChangChien CC, Lin H, et al. Can a preoperative CA 125 level be a criterion for full pelvic lymphadenectomy in surgical staging of endometrial cancer? Gynecol Oncol. 2002;86:28–33.CrossRefPubMed Hsieh CH, ChangChien CC, Lin H, et al. Can a preoperative CA 125 level be a criterion for full pelvic lymphadenectomy in surgical staging of endometrial cancer? Gynecol Oncol. 2002;86:28–33.CrossRefPubMed
10.
go back to reference Powell JL, Hill KA, Shiro BC, Diehl SJ, Gajewski WH. Preoperative CA 125 levels in treating endometrial cancer. J Reprod Med. 2005;50:585–90.PubMed Powell JL, Hill KA, Shiro BC, Diehl SJ, Gajewski WH. Preoperative CA 125 levels in treating endometrial cancer. J Reprod Med. 2005;50:585–90.PubMed
11.
go back to reference Yurkovetsky Z, Ta’asan S, Skates S, et al. Development of multi-marker panel for early detection of endometrial cancer: High diagnostic power of prolactin. Gynecol Oncol. 2007;107:58–65.PubMedCentralCrossRefPubMed Yurkovetsky Z, Ta’asan S, Skates S, et al. Development of multi-marker panel for early detection of endometrial cancer: High diagnostic power of prolactin. Gynecol Oncol. 2007;107:58–65.PubMedCentralCrossRefPubMed
12.
go back to reference Moore RG, Brown A, Miller M, Skaters S, Allard W, Verch T, et al. The use of multiple novel biomarkers for the detection of ovarian carcinoma in patients with pelvic mass. Gynecol Oncol. 2008;108:402–8.CrossRefPubMed Moore RG, Brown A, Miller M, Skaters S, Allard W, Verch T, et al. The use of multiple novel biomarkers for the detection of ovarian carcinoma in patients with pelvic mass. Gynecol Oncol. 2008;108:402–8.CrossRefPubMed
13.
go back to reference Bingle L, Cross SS, High AS, Wallace WA, Rassl D, Yuan G, et al. WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung. Respir Res. 2006;7:61.PubMedCentralCrossRefPubMed Bingle L, Cross SS, High AS, Wallace WA, Rassl D, Yuan G, et al. WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung. Respir Res. 2006;7:61.PubMedCentralCrossRefPubMed
14.
go back to reference Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is over expressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65:2162–9.CrossRefPubMed Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is over expressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65:2162–9.CrossRefPubMed
15.
go back to reference Huhtinen K, Suvitie P, Hiissa J, Huvila J, Kujari H, Stala M, et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 2009;100:1315–9.PubMedCentralCrossRefPubMed Huhtinen K, Suvitie P, Hiissa J, Huvila J, Kujari H, Stala M, et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 2009;100:1315–9.PubMedCentralCrossRefPubMed
16.
go back to reference Galgano M, Hampton G, Frierson HJ. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol. 2006;19:847–553.PubMed Galgano M, Hampton G, Frierson HJ. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol. 2006;19:847–553.PubMed
17.
go back to reference Bignotti E, Ragnoli M, Zanotti L, et al. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients. Br J Cancer. 2011;104:1418–25.PubMedCentralCrossRefPubMed Bignotti E, Ragnoli M, Zanotti L, et al. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients. Br J Cancer. 2011;104:1418–25.PubMedCentralCrossRefPubMed
18.
go back to reference Zanotti L, Bignotti E, Calza S, et al. Human epididymis protein 4 as a serum marker for diagnosis of endometrial carcinoma and prediction of clinical outcome. Clin Chem Lab Med. 2012;50:2189–98.CrossRefPubMed Zanotti L, Bignotti E, Calza S, et al. Human epididymis protein 4 as a serum marker for diagnosis of endometrial carcinoma and prediction of clinical outcome. Clin Chem Lab Med. 2012;50:2189–98.CrossRefPubMed
19.
go back to reference Mutz-Dehbalaie I, Egle D, Fessler S, et al. HE4 is an independent prognostic marker in endometrial cancer patients. Gynecol Oncol. 2012;126:186–91.CrossRefPubMed Mutz-Dehbalaie I, Egle D, Fessler S, et al. HE4 is an independent prognostic marker in endometrial cancer patients. Gynecol Oncol. 2012;126:186–91.CrossRefPubMed
20.
go back to reference Mutch DG. The New FIGO staging system for cancers of the vulva, cervix, endometrium, and sarcomas. Gynecol Oncol. 2009;115:325–8.CrossRef Mutch DG. The New FIGO staging system for cancers of the vulva, cervix, endometrium, and sarcomas. Gynecol Oncol. 2009;115:325–8.CrossRef
21.
go back to reference Ueda Y, Enomoto T, Kimura T, Miyatake T, Yoshino K, Fujita M, et al. Serum biomarkers for early detection of gynecologic cancers. Cancer. 2010;2:1312–7.CrossRef Ueda Y, Enomoto T, Kimura T, Miyatake T, Yoshino K, Fujita M, et al. Serum biomarkers for early detection of gynecologic cancers. Cancer. 2010;2:1312–7.CrossRef
22.
go back to reference Hellstrom I, Raycraft J, Hayden-Ledbetter JA, Schummer M, McIntosh M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003;63:3695–700.PubMed Hellstrom I, Raycraft J, Hayden-Ledbetter JA, Schummer M, McIntosh M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003;63:3695–700.PubMed
23.
go back to reference Sood AK, Buller RE, Burger RA, et al. Value of preoperative CA 125 level in the management of uterine cancer and prediction of outcome. Obstet Gynecol. 1997;90:441–7.CrossRefPubMed Sood AK, Buller RE, Burger RA, et al. Value of preoperative CA 125 level in the management of uterine cancer and prediction of outcome. Obstet Gynecol. 1997;90:441–7.CrossRefPubMed
24.
go back to reference Koper NP, Massuger LF, Thomas CM, Kiemeney LA, Verbeek AL. Serum CA 125 measurements to identify patients with endometrial cancer who require lymphadenectomy. Anticancer Res. 1998;18:1897–902.PubMed Koper NP, Massuger LF, Thomas CM, Kiemeney LA, Verbeek AL. Serum CA 125 measurements to identify patients with endometrial cancer who require lymphadenectomy. Anticancer Res. 1998;18:1897–902.PubMed
25.
go back to reference Chung HH, Kim JW, Park NH, Song YS, et al. Use of preoperative serum CA-125 levels for prediction of lymph node metastasis and prognosis in endometrial cancer. Acta Obstet Gynecol. 2006;85:1501–5.CrossRef Chung HH, Kim JW, Park NH, Song YS, et al. Use of preoperative serum CA-125 levels for prediction of lymph node metastasis and prognosis in endometrial cancer. Acta Obstet Gynecol. 2006;85:1501–5.CrossRef
26.
go back to reference Rustin GJ, Bast RC, Kelloff GJ, et al. Use of CA-125 in clinical trial evaluation of new therapeutic drugs for ovarian cancer. Clin Cancer Res. 2004;10:3919–26.CrossRefPubMed Rustin GJ, Bast RC, Kelloff GJ, et al. Use of CA-125 in clinical trial evaluation of new therapeutic drugs for ovarian cancer. Clin Cancer Res. 2004;10:3919–26.CrossRefPubMed
27.
go back to reference Li J, Dowdy S, Tipton T, Podratz K, Lu W-G, Xie X, et al. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn. 2009;9:555–66.PubMedCentralCrossRefPubMed Li J, Dowdy S, Tipton T, Podratz K, Lu W-G, Xie X, et al. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn. 2009;9:555–66.PubMedCentralCrossRefPubMed
28.
go back to reference Iwahori K, Suzuki H, Kishi Y, Fujii Y, Uehara R, Okamoto N, et al. Serum HE4 as a diagnostic and prognostic marker for lung cancer. Tumour Biol. 2012;33:1141–9.CrossRefPubMed Iwahori K, Suzuki H, Kishi Y, Fujii Y, Uehara R, Okamoto N, et al. Serum HE4 as a diagnostic and prognostic marker for lung cancer. Tumour Biol. 2012;33:1141–9.CrossRefPubMed
29.
go back to reference Yoo S-C, Yoon J-H, Kim WY, Chang S-J, Joo H-J, Ryu G-S. Premenopausal early-stage endometrial carcinoma patients with low CA-125 levels and low tumor grade may undergo ovary-saving surgery. J Gynecol Oncol. 2009;20:181–6.PubMedCentralCrossRefPubMed Yoo S-C, Yoon J-H, Kim WY, Chang S-J, Joo H-J, Ryu G-S. Premenopausal early-stage endometrial carcinoma patients with low CA-125 levels and low tumor grade may undergo ovary-saving surgery. J Gynecol Oncol. 2009;20:181–6.PubMedCentralCrossRefPubMed
30.
31.
go back to reference Sebastianelli A, Renaud MC, Gregorie J, Roy M, Plante M. Preoperative CA 125 tumour marker in endometrial cancer: correlation with advanced stage disease. J Obstet Gynaecol Can. 2010;32:856–60.PubMed Sebastianelli A, Renaud MC, Gregorie J, Roy M, Plante M. Preoperative CA 125 tumour marker in endometrial cancer: correlation with advanced stage disease. J Obstet Gynaecol Can. 2010;32:856–60.PubMed
32.
go back to reference Moore RG, Jabre-Raughley M, Brown AK, Robison KM, Miller C, Allard WJ, et al. Comparison of a novel multiple marker assay vs the risk of malignancy index for the prediction of epithelial ovarian cancer in patients with pelvic mass. Am J Obstet Gynecol. 2010;203:228e1–6.CrossRef Moore RG, Jabre-Raughley M, Brown AK, Robison KM, Miller C, Allard WJ, et al. Comparison of a novel multiple marker assay vs the risk of malignancy index for the prediction of epithelial ovarian cancer in patients with pelvic mass. Am J Obstet Gynecol. 2010;203:228e1–6.CrossRef
34.
go back to reference Khan N, Cromer CJ, Campa M, Patz Jr EF. Clinical utility of serum amyloid A and macrophage migration inhibitory factor as serum biomarkers for detection of nonsmall cell lung carcinoma. Cancer. 2004;101:379–84.CrossRefPubMed Khan N, Cromer CJ, Campa M, Patz Jr EF. Clinical utility of serum amyloid A and macrophage migration inhibitory factor as serum biomarkers for detection of nonsmall cell lung carcinoma. Cancer. 2004;101:379–84.CrossRefPubMed
Metadata
Title
The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients
Authors
Beyhan Omer
Sema Genc
Ozguc Takmaz
Ahmet Dirican
Zeynep Kusku-Kiraz
Sinan Berkman
Figen Gurdol
Publication date
01-10-2013
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2013
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-0814-z

Other articles of this Issue 5/2013

Tumor Biology 5/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine