The importance of HE4 in differential diagnosis of endometrial cancer
Authors:
Luboš Minář 1
; I. Klabenešová 2; E. Jandáková 3
Authors‘ workplace:
Gynekologicko-porodnická klinika LF MU a FN, Brno, přednosta prof. MUDr. P. Ventruba, DrSc.
1; Oddělení klinické biochemie FN, Brno, primář doc. MUDr. M. Dastych, CSc.
2; Ústav patologie LF MU a FN, Brno, přednosta doc. MUDr. L. Křen, PhD.
3
Published in:
Ceska Gynekol 2015; 80(4): 256-263
Overview
Objective:
The aim of the present study was to evaluate the use of human epididymis protein 4 (HE4) and cancer antigen 125 (CA 125) biomarkers in differential diagnosis of malignant and benign endometrial tumours in a population of Czech women.
Design:
Prospective study.
Setting:
Department of Gynaecology and Obstetrics, Faculty of Medicine at Masaryk University and Faculty Hospital in Brno.
Methods:
Our prospective study includes 115 patients with endometrioid adenocarcinoma and 106 patients with benign endometrial tumours in the control group. They were diagnosed with endometrial biopsy in the period from 7/2010 to 6/2013. The patients with cancer underwent definitive surgical treatment to determine the stage of disease. The median and ranges of serum levels were determined in relation to the histological result (benign vs malignant disease). Statistical analysis operates with logarithm values of markers because their distribution is not normal and uses logistic regression.
Results:
While analysing two groups of patients with different histology, there was demonstrated a statistically significant difference (p < 0.05), only in HE4, by cut-off 48,5 pmol/l there was achieved sensitivity of 87.8%, specificity of 56.6% and negative predictive value of 81.1%.
Coclusion:
Diagnostic benefit of HE4 can be considered especially in patients with increased risk of endometrial cancer and in patients with serious internal co-morbidities. HE4 could help in combination with clinical and ultrasound finding in the differentiation of prognostically various groups of patients and in decision-making in relation to the individualization of the treatment plan. However, the optimal cut-off for HE4 has not been solved yet, and to do so, it will require more research with larger studies and their comparative analysis..
Keywords:
benign endometrial tumours, endometrial cancer, human epididymis protein 4 (HE4), cancer antigen 125 (CA 125), surgical staging, stage of disease
Sources
1. Adam, Z., Vorlíček, J., Vaníček, J., et al. Diagnostické a léčebné postupy u maligních chorob. Praha: Grada Publishing, 2004, s. 231–235.
2. Angioli, R., Plotti, F., Capriglione, S., et al. The role of novel biomarker HE4 in endometrial cancer: a case control prospective study. Tumour Biol, 2013, 34(1), p. 571–576.
3. Bingle, L., Singleton, V., Bingle, CD. The putative ovarian tumor marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes komplex alternative splicing to yield multiple protein isoforms. Oncogene, 2002, 21(17), p. 2768–2773.
4. Bouchard, D., Morriset, D., Bourbonnais, Y., et al. Proteins with whey-acidic-protein motifs and cancer. Lancet Oncol, 2006, 7(2), p. 167–174.
5. Budíková, M., Králová, M., Maroš, B. Průvodce základními statistickými metodami. Praha: Grada Publishing, 2010, p. 193–204.
6. DiSaia, PJ., Creasman, WT. Clinical Gynaecologic Oncology. 7th ed. Philadelphia: Mosby, 2007, p. 812.
7. Drapkin, R., von Horsten, HH., Lin, Y., et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovaria carcinomas. Cancer Res, 2005, 65(6), p. 2162–2169.
8. Dundr, P. Histopatologická klasifikace nádorů děložního těla In: Cibula, D., Petruželka, L., et al. Onkogynekologie. Praha: Grada Publishing, 2009, s. 459.
9. Dušek, L., Mužík, J., Kubásek, M., et al. Epidemiologie zhoubných nádorů v České republice [online]. Masarykova univerzita, [2005], [cit. 2014-07-14]. Dostupný z : http://www.svod.cz.
10. Ebina, Y., Sakuragi, N., Hareyama, H., et al. Para-aortic lymphnode metastasis in relation to serum CA 125 levels and nuclear grade in endometrial carcinoma. Acta Obstet Gynecol Scand, 2002, 81(5), p. 458–465.
11. Engelen, MJ., Kos, HE., Willemse, PH., et al. Surgery by consultant gynecologic oncologists improves survival in patiens with ovarian carcinoma. Cancer, 2006 106(3), p. 589–598.
12. Farias-Eisner, G., Su, F., Robbins, T., et al. Validation of serum biomarkers for detection of early- and ate-stage endometrial cancer. Am J Obstet Gynecol, 2010, 202(1), p. 73.e1–73.e5.
13. Galgano, MT., Hampton, GM., Frierson, HF. jr. Compre-hensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol, 2006, 19(6), p. 847–853.
14. Hellström, I., Raycraft, J., Hayden-Ledbetter, M., et al. The HE4 (WFCD2) protein is a biomarker for ovarian carcinoma. Cancer Res, 2003, 63(13), p. 3695–3700.
15. Cherchi, PL., Dessole, S., Ruiu, GA., et al. The value of serum CA 125 and association CA 125/CA19-9 in endometrial carcinoma. Eur J Gynecol Oncol, 1999, 20(4), p. 315–317.
16. Chung, HH., Kim, JW., Park, NH., et al. Use of preoperative serum CA 125 levels for prediction of lymph node metastasis and prognosis in endometrial cancer. Acta Obstet Gynecol Scand, 2006, 85(12), p. 1501–1505.
17. Israeli, O., Goldring-Aviram, A., Rienstein, S., et al. In silico chromosomal clustering of genes displaying altered expression patterns in ovarian cancer. Cancer Genet Cytogenet, 2005, 160(1), p. 35–42.
18. Kirchoff, C. Molecular characterization od epididymal proteins. Rev Reprod, 1998, 3(2), p. 86–95.
19. Kirchhoff, C., Habben, I., Ivell, R., et al. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod, 1991, 45(2), p. 350–357.
20. Klener, P. Klinická onkologie. Praha: Galén, 2002, s. 85–88.
21. Masák, L. Sérové nádorové markery. In Cibula, D., Petružel-ka, L., et al. Onkogynekologie. Praha: Grada Publishing, 2009, s. 132–141.
22. Moore, RG., Brown, AK., Miller, MC., et al. Utility of a novel serum tumor biomarker HE4 in patients with endome-trioid adenocarcinoma of the uterus. Gynecol Oncol, 2008, 110(2), p. 196–201.
23. Moore, RG., Miller, MC., Disilvestro, P., et al. Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet Gynecol, 2011, 118(2, Pt 1), p. 280–288.
24. Omer, B., Genc, S., Takmaz, O., et al. The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients. Tumour Biol, 2013, 34(5), p. 2645–2650.
25. Yurkovetsky, Z., Ta’asan, S., Skates, S., et al. Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin. Gynecol Oncol, 2007, 107(1), p. 58–65.
26. 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(12), p. 2189–2198.
27. http://www-dep.iarc.fr/usefullinks/NationalCancerInsti-tute(USA)/EndometrialCancer.
28. http://www.wikiskripta.eu/index.php/ROC křivka.
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