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Published in: Tumor Biology 2/2014

01-02-2014 | Review

A critical review on HE4 performance in endometrial cancer: where are we now?

Authors: Roberto Angioli, Andrea Miranda, Alessia Aloisi, Roberto Montera, Stella Capriglione, Carlo De Cicco Nardone, Corrado Terranova, Francesco Plotti

Published in: Tumor Biology | Issue 2/2014

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Abstract

To date, no good marker for endometrial cancer (EC) that may be routinely used in clinical practice for diagnosis, prognosis and monitoring is available; besides the use of tumour markers is not recommended by international guidelines. However, during the last years, an increasing interest in literature has been growing on human epididymis protein 4 (HE4) that demonstrated to be a useful clinical marker with high sensitivity and specificity even at early stage. However, published studies differ for some variables such as HE4 cut-off and sample size. Therefore, we assess this comprehensive review to gather all the evidence reported in literature on HE4 potential value in diagnosis, prognosis, and recurrence of EC. A systematic literature search was performed using PubMed/PubMed Central/MEDLINE predefined keywords from January 1952 to June 2013. We divided all the relevant studies into three different clinical issues: “Diagnosis”, “Prognosis” and “Disease monitoring”. The analysis of published data suggests that HE4 is the most accurate and sensitive EC marker identified to date. In particular, this new marker seems to have a good performance in diagnosis. The best cut-off of HE4 in diagnosis ranges between 50 and 70 pmol/L, resulting at least in 78.8 % of sensitivity and 100 % of specificity in all stages. Another important aspect to consider is HE4 capacity in predicting the stage of disease and myometrial involvement, which can help scheduling the appropriate timing of imaging and surgery in a more individualised fashion and as indicator of patients prognosis.
Literature
1.
2.
go back to reference Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Wárlám-Rodenhuis CC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post operative radiation therapy in endometrial carcinoma. Lancet. 2000;355(9213):1404–11.PubMedCrossRef Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Wárlám-Rodenhuis CC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post operative radiation therapy in endometrial carcinoma. Lancet. 2000;355(9213):1404–11.PubMedCrossRef
3.
go back to reference Papanikolaou A, Kalogiannidis I, Goutzioulis M, Misailidou D, Makedos A, Vergote I, et al. Pelvic lymphadenectomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer. Arch Gynecol Obstet. 2006;274(2):91–6.PubMedCrossRef Papanikolaou A, Kalogiannidis I, Goutzioulis M, Misailidou D, Makedos A, Vergote I, et al. Pelvic lymphadenectomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer. Arch Gynecol Obstet. 2006;274(2):91–6.PubMedCrossRef
4.
go back to reference Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol. 2004;24(5):558–65.PubMedCrossRef Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol. 2004;24(5):558–65.PubMedCrossRef
5.
go back to reference Li J, Dowdy S, Tipton T, Podratz K, Lu WG, Xie X, et al. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn. 2009;9(6):555–66.PubMedCentralPubMedCrossRef Li J, Dowdy S, Tipton T, Podratz K, Lu WG, Xie X, et al. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn. 2009;9(6):555–66.PubMedCentralPubMedCrossRef
6.
go back to reference Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, Longacre TA, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer. 2006;94(5):642–6.PubMedCentralPubMed Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, Longacre TA, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer. 2006;94(5):642–6.PubMedCentralPubMed
7.
go back to reference Fujimoto T, Nanjyo H, Fukuda J, Nakamura A, Mizunuma H, Yaegashi N, et al. Endometrioid uterine cancer: histopathological risk factors of local and distant recurrence. Gynecol Oncol. 2009;112(2):342–7.PubMedCrossRef Fujimoto T, Nanjyo H, Fukuda J, Nakamura A, Mizunuma H, Yaegashi N, et al. Endometrioid uterine cancer: histopathological risk factors of local and distant recurrence. Gynecol Oncol. 2009;112(2):342–7.PubMedCrossRef
8.
go back to reference Hernandez E. American college of obstericians and gynecologists. ACOG practice bulletin number 65: management of endometrial cancer. Obstet Gynecol. 2006;107(4):952.PubMedCrossRef Hernandez E. American college of obstericians and gynecologists. ACOG practice bulletin number 65: management of endometrial cancer. Obstet Gynecol. 2006;107(4):952.PubMedCrossRef
9.
go back to reference Emons G, Kimmig R. Uterus commission of the gynecological oncology working group (AGO). Interdisciplinary S2k guidelines on the diagnosis and treatment of endometrial carcinoma. J Cancer Res Clin Oncol. 2009;135(10):1387–91.PubMedCentralPubMedCrossRef Emons G, Kimmig R. Uterus commission of the gynecological oncology working group (AGO). Interdisciplinary S2k guidelines on the diagnosis and treatment of endometrial carcinoma. J Cancer Res Clin Oncol. 2009;135(10):1387–91.PubMedCentralPubMedCrossRef
10.
go back to reference Ward JH. NCCN guidelines and the international community. J Natl Compr Canc Netw. 2011;9(2):133–4.PubMed Ward JH. NCCN guidelines and the international community. J Natl Compr Canc Netw. 2011;9(2):133–4.PubMed
11.
go back to reference Moore RG, Brown AK, Miller MC, Badgwell D, Lu Z, Allard WJ, 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.PubMedCentralPubMedCrossRef Moore RG, Brown AK, Miller MC, Badgwell D, Lu Z, Allard WJ, 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.PubMedCentralPubMedCrossRef
12.
go back to reference Bignotti E, Ragnoli M, Zanotti L, Calza S, Falchetti M, Lonardi S, et al. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients. Br J Cancer. 2011;104(9):1418–25.PubMedCentralPubMedCrossRef Bignotti E, Ragnoli M, Zanotti L, Calza S, Falchetti M, Lonardi S, et al. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients. Br J Cancer. 2011;104(9):1418–25.PubMedCentralPubMedCrossRef
13.
go back to reference Moore RG, Miller CM, Brown AK, Robison K, Steinhoff M, Lambert-Messerlian G. Utility of tumor marker HE4 to predict depth of myometrial invasion in endometrioid adenocarcinoma of the uterus. Int J Gynecol Cancer. 2011;21(7):1185–90.PubMed Moore RG, Miller CM, Brown AK, Robison K, Steinhoff M, Lambert-Messerlian G. Utility of tumor marker HE4 to predict depth of myometrial invasion in endometrioid adenocarcinoma of the uterus. Int J Gynecol Cancer. 2011;21(7):1185–90.PubMed
14.
go back to reference Kalogera E, Scholler N, Powless C, Weaver A, Drapkin R, Li J, et al. Correlation of serum HE4 with tumor size and myometrial invasion in endometrial cancer. Gynecol Oncol. 2012;124(2):270–5.PubMedCentralPubMedCrossRef Kalogera E, Scholler N, Powless C, Weaver A, Drapkin R, Li J, et al. Correlation of serum HE4 with tumor size and myometrial invasion in endometrial cancer. Gynecol Oncol. 2012;124(2):270–5.PubMedCentralPubMedCrossRef
15.
go back to reference Mutz-Dehbalaie I, Egle D, Fessler S, Hubalek M, Fiegl H, Marth C, et al. HE4 is an independent prognostic marker in endometrial cancer patients. Gynecol Oncol. 2012;126(2):186–91.PubMedCrossRef Mutz-Dehbalaie I, Egle D, Fessler S, Hubalek M, Fiegl H, Marth C, et al. HE4 is an independent prognostic marker in endometrial cancer patients. Gynecol Oncol. 2012;126(2):186–91.PubMedCrossRef
16.
go back to reference Zanotti L, Bignotti E, Calza S, Bandiera E, Ruggeri G, Galli C, 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):2189–98.PubMedCrossRef Zanotti L, Bignotti E, Calza S, Bandiera E, Ruggeri G, Galli C, 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):2189–98.PubMedCrossRef
17.
go back to reference Angioli R, Plotti F, Capriglione S, Montera R, Damiani P, Ricciardi R, et al. The role of novel biomarker HE4 in endometrial cancer: a case control prospective study. Tumour Biol. 2013;34(1):571–6.PubMedCrossRef Angioli R, Plotti F, Capriglione S, Montera R, Damiani P, Ricciardi R, et al. The role of novel biomarker HE4 in endometrial cancer: a case control prospective study. Tumour Biol. 2013;34(1):571–6.PubMedCrossRef
18.
go back to reference Saarelainen SK, Peltonen N, Lehtimäki T, Perheentupa A, Vuento MH, Mäenpää JU. Predictive value of serum human epididymis protein 4 and cancer antigen 125 concentrations in endometrial carcinoma. Am J Obstet Gynecol. 2013;209(2):142. e1–6.PubMedCrossRef Saarelainen SK, Peltonen N, Lehtimäki T, Perheentupa A, Vuento MH, Mäenpää JU. Predictive value of serum human epididymis protein 4 and cancer antigen 125 concentrations in endometrial carcinoma. Am J Obstet Gynecol. 2013;209(2):142. e1–6.PubMedCrossRef
19.
go back to reference Omer B, Genc S, Takmaz O, Dirican A, Kusku-Kiraz Z, Berkman S, Gurdol F. The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients. Tumour Biol. 2013 May 3. Omer B, Genc S, Takmaz O, Dirican A, Kusku-Kiraz Z, Berkman S, Gurdol F. The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients. Tumour Biol. 2013 May 3.
20.
21.
go back to reference Kew FM, Roberts AP, Cruickshank DJ. The role of routine follow-up after gynecological malignancy. Int J Gynecol Cancer. 2005;15(3):413–9.PubMedCrossRef Kew FM, Roberts AP, Cruickshank DJ. The role of routine follow-up after gynecological malignancy. Int J Gynecol Cancer. 2005;15(3):413–9.PubMedCrossRef
22.
go back to reference Lajer H, Jensen MB, Kilsmark J, Albæk J, Svane D, Mirza MR, et al. The value of gynecologic cancer follow-up: evidence-based ignorance? Int J Gynecol Cancer. 2010;20(8):1307–20.PubMed Lajer H, Jensen MB, Kilsmark J, Albæk J, Svane D, Mirza MR, et al. The value of gynecologic cancer follow-up: evidence-based ignorance? Int J Gynecol Cancer. 2010;20(8):1307–20.PubMed
23.
go back to reference Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;95 Suppl 1:105–43.CrossRef Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;95 Suppl 1:105–43.CrossRef
Metadata
Title
A critical review on HE4 performance in endometrial cancer: where are we now?
Authors
Roberto Angioli
Andrea Miranda
Alessia Aloisi
Roberto Montera
Stella Capriglione
Carlo De Cicco Nardone
Corrado Terranova
Francesco Plotti
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1190-4

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