open access

Vol 4, No 4 (2019)
Original article
Published online: 2019-12-05
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The assessment of usefulness of HE4 and CA125 quantification for the diagnostics of endometrial cancer

Marta Zalewska-Zacharek1, Jolanta Zegarska1, Lena Nowak-Łoś1, Magdalena Kuligowska-Prusińska1, Grażyna Odrowąż-Sypniewska1, Marek Grabiec1, Karina Chmielarz1
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Medical Research Journal 2019;4(4):201-209.
Affiliations
  1. Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland

open access

Vol 4, No 4 (2019)
ORIGINAL ARTICLES
Published online: 2019-12-05

Abstract

Endometrial cancer is one of the most prevalent uterine malignancies. This disease occurs mostly in older women, frequently affected with other comorbidities. Hence, it is important to search for novel, less burdensome diagnostic modalities, enabling the objective assessment of the patient’s status and facilitating qualification to relevant risk groups prior to surgical treatment.
The aim of this study was to verify the usefulness of CA125 and HE4 in the evaluation of endometrial cancer.
The study included 308 women treated at University Hospital No. 2 in Bydgoszcz. The study group included 180 patients operated due to endometrial cancer. The control group included 128 women operated due to perineal statics disorders. The concentrations of tumour markers were measured with ELISA-based ready-to-use diagnostic kits.
Patients with endometrial cancer and healthy women differed significantly in terms of HE4 concentrations (P = 0.001). The serum concentration of HE4 in stage I endometrial cancer patients was significantly higher (Me = 88.37 pM) than in healthy women (Me = 46.14) (P = 0.007). The analysis of ROC curves with the determination of the area under curve showed 66.7% sensitivity and 78.1% specificity of HE4. AUC for HE4 amounted to 0.721 and was the highest of all markers.
Our analysis revealed that HE4 is useful in the detection of endometrial cancer, while Human Epididymis Protein 4 can potentially be used for screening purposes. CA125 antigen, previously used in the diagnostic process, is useless or may possess limited usefulness. There is a need for further studies on larger populations of female patients.

Abstract

Endometrial cancer is one of the most prevalent uterine malignancies. This disease occurs mostly in older women, frequently affected with other comorbidities. Hence, it is important to search for novel, less burdensome diagnostic modalities, enabling the objective assessment of the patient’s status and facilitating qualification to relevant risk groups prior to surgical treatment.
The aim of this study was to verify the usefulness of CA125 and HE4 in the evaluation of endometrial cancer.
The study included 308 women treated at University Hospital No. 2 in Bydgoszcz. The study group included 180 patients operated due to endometrial cancer. The control group included 128 women operated due to perineal statics disorders. The concentrations of tumour markers were measured with ELISA-based ready-to-use diagnostic kits.
Patients with endometrial cancer and healthy women differed significantly in terms of HE4 concentrations (P = 0.001). The serum concentration of HE4 in stage I endometrial cancer patients was significantly higher (Me = 88.37 pM) than in healthy women (Me = 46.14) (P = 0.007). The analysis of ROC curves with the determination of the area under curve showed 66.7% sensitivity and 78.1% specificity of HE4. AUC for HE4 amounted to 0.721 and was the highest of all markers.
Our analysis revealed that HE4 is useful in the detection of endometrial cancer, while Human Epididymis Protein 4 can potentially be used for screening purposes. CA125 antigen, previously used in the diagnostic process, is useless or may possess limited usefulness. There is a need for further studies on larger populations of female patients.

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Keywords

endometrial cancer; endometrial carcinoma; HE4; CA125; biomarkers; tumour; diagnostics

About this article
Title

The assessment of usefulness of HE4 and CA125 quantification for the diagnostics of endometrial cancer

Journal

Medical Research Journal

Issue

Vol 4, No 4 (2019)

Article type

Original article

Pages

201-209

Published online

2019-12-05

Page views

1020

Article views/downloads

687

DOI

10.5603/MRJ.a2019.0036

Bibliographic record

Medical Research Journal 2019;4(4):201-209.

Keywords

endometrial cancer
endometrial carcinoma
HE4
CA125
biomarkers
tumour
diagnostics

Authors

Marta Zalewska-Zacharek
Jolanta Zegarska
Lena Nowak-Łoś
Magdalena Kuligowska-Prusińska
Grażyna Odrowąż-Sypniewska
Marek Grabiec
Karina Chmielarz

References (30)
  1. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol. 2012; 3(2): 105–119.
  2. Scurry J, Brand A, Sheehan P, et al. High-grade endometrial carcinoma in secretory endometrium in young women: a report of five cases. Gynecol Oncol. 1996; 60(2): 224–227.
  3. Kaku T, Matsuo K, Tsukamoto N, et al. Endometrial carcinoma in women aged 40 years or younger: a Japanese experience. Int J Gynecol Cancer. 1993; 3(3): 147–153.
  4. Ueda SM, Kapp DS, Cheung MK, et al. Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths. Am J Obstet Gynecol. 2008; 198(2): 218.e1–218.e6.
  5. Koss LG, Schreiber K, Oberlander SG, et al. Detection of endometrial carcinoma and hyperplasia in asymptomatic women. Obstet Gynecol. 1984; 64(1): 1–11.
  6. Wright TC, Massad LS, Dunton CJ, et al. 2006 American Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007; 197(4): 346–355.
  7. Ragni N, Ferrero S, Prefumo F, et al. The association between p53 expression, stage and histological features in endometrial cancer. Eur J Obstet Gynecol Reprod Biol. 2005; 123(1): 111–116.
  8. Keys HM, Roberts JA, Brunetto VL, et al. Gynecologic Oncology Group. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004; 92(3): 744–751.
  9. Creutzberg CL, van Putten WLJ, Koper PC, et al. PORTEC Study Group. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003; 89(2): 201–209.
  10. Fung-Kee-Fung M, Dodge J, Elit L, et al. Cancer Care Ontario Program in Evidence-based Care Gynecology Cancer Disease Site Group. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. 2006; 101(3): 520–529.
  11. Galgano MT, Hampton GM, Frierson HF. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol. 2006; 19(6): 847–853.
  12. Kalogera E, Scholler N, Powless C, et al. Correlation of serum HE4 with tumor size and myometrial invasion in endometrial cancer. Gynecol Oncol. 2012; 124(2): 270–275.
  13. Moore RG, Brown AK, Miller MC, et al. Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus. Gynecol Oncol. 2008; 110(2): 196–201.
  14. Zhang Am, Zhang P. [Clinical value of combined detection of serum human epididymal secretory protein E4 and CA(125) in the diagnosis of endometrial carcinoma]. Zhonghua Fu Chan Ke Za Zhi. 2012; 47(2): 125–128.
  15. 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(9): 1418–1425.
  16. Mutz-Dehbalaie I, Egle D, Fessler S, et al. HE4 is an independent prognostic marker in endometrial cancer patients. Gynecol Oncol. 2012; 126(2): 186–191.
  17. Li J, Dowdy S, Tipton T, et al. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn. 2009; 9(6): 555–566.
  18. Sebastianelli A, Renaud MC, Grégoire J, et al. Preoperative CA 125 tumour marker in endometrial cancer: correlation with advanced stage disease. J Obstet Gynaecol Can. 2010; 32(9): 856–860.
  19. Ginath S, Menczer J, Fintsi Y, et al. Tissue and serum CA125 expression in endometrial cancer. Int J Gynecol Cancer. 2002; 12(4): 372–375.
  20. Gadducci A, Cosio S, Carpi A, et al. Serum tumor markers in the management of ovarian, endometrial and cervical cancer. Biomed Pharmacother. 2004; 58(1): 24–38.
  21. Kim HS, Park CY, Lee JM, et al. Evaluation of serum CA-125 levels for preoperative counseling in endometrioid endometrial cancer: a multi-center study. Gynecol Oncol. 2010; 118(3): 283–288.
  22. Powell JL, Hill KA, Shiro BC, et al. Preoperative serum CA-125 levels in treating endometrial cancer. J Reprod Med. 2005; 50(8): 585–590.
  23. Nicklin J, Janda M, Gebski V, et al. LACE Trial Investigators. The utility of serum CA-125 in predicting extra-uterine disease in apparent early-stage endometrial cancer. Int J Cancer. 2012; 131(4): 885–890.
  24. Cho H, Kang ES, Kim YT, et al. Diagnostic and prognostic impact of osteopontin expression in endometrial cancer. Cancer Invest. 2009; 27(3): 313–323.
  25. Dvalishvili I, Charkviani L, Turashvili G, et al. Clinical characteristics of prognostic factors in uterine endometrioid adenocarcinoma of various grade. Georgian Med News. 2006(132): 24–27.
  26. Dotters DJ. Preoperative CA 125 in endometrial cancer: is it useful? Am J Obstet Gynecol. 2000; 182(6): 1328–1334.
  27. Molina R, Escudero JM, Augé JM, et al. HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases. Tumour Biol. 2011; 32(6): 1087–1095.
  28. Bolstad N, Øijordsbakken M, Nustad K, et al. Human epididymis protein 4 reference limits and natural variation in a Nordic reference population. Tumour Biol. 2012; 33(1): 141–148.
  29. Lenhard M, Stieber P, Hertlein L, et al. The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses. Clin Chem Lab Med. 2011; 49(12): 2081–2088.
  30. Kim BoW, Jeon YE, Cho H, et al. Pre-treatment diagnosis of endometrial cancer through a combination of CA125 and multiplication of neutrophil and monocyte. J Obstet Gynaecol Res. 2012; 38(1): 48–56.

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