Skip to main content
Erschienen in: Tumor Biology 6/2015

01.06.2015 | Research Article

Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study

verfasst von: Stella Capriglione, Francesco Plotti, Andrea Miranda, Roberto Ricciardi, Giuseppe Scaletta, Alessia Aloisi, Federica Guzzo, Roberto Montera, Roberto Angioli

Erschienen in: Tumor Biology | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

This study aims to investigate the correlation between preoperative human epididymis protein 4 (HE4) levels, endometrial cancer (EC) staging, and ideal cutoff for stage prediction. All EC patients, treated within January 2009 and February 2014 at the Division of Gynaecologic Oncology of the University Campus Bio-Medico of Rome, were considered for the study. For the first part of the study, we consider an HE4 cutoff of 70 pmol/L. Histotypes (endometrioid versus non-endometrioid), grading (G1, G2, G3), and stage were correlated with HE4 levels. In the second part of the study, the logistic regression was performed in stepwise mood to identify the ideal HE4 cutoff for stage prediction. Two hundred thirty-two patients with surgically staged EC and preoperative HE4 dosage were included in the study. We found that higher HE4 levels correlate with undifferentiated grading (p < 0.05). Moreover, we found that 42, 77, 90, 93 and 100 % of patients classified as International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, II, III, and IV, respectively, presented HE4 levels above the standard cutoff of 70 pmol/L. Based on receiver operating characteristic (ROC) curves, we found the ideal HE4 cutoff as follows: 61.3 pmol/L for FIGO stage IA (sensitivity = 82.3 % and specificity = 96 %), 89.2 pmol/L for FIGO stage IB (sensitivity = 83.3 % and specificity = 96 %), 104.3 pmol/L for FIGO stage II (sensitivity = 80.9 % and specificity = 98.6 %), 152.6 pmol/L for FIGO stage III (sensitivity = 92.5 % and specificity = 98.6 %), and 203.8 pmol/L for FIGO stage IV (sensitivity = 81.8 % and specificity = 99.3 %). Our results suggest a potential role of HE4 in EC stage prediction.
Literatur
1.
Zurück zum Zitat Creasman WT. FIGO stage 1988 revision. GynecolOncol. 1989;35:125–7. Creasman WT. FIGO stage 1988 revision. GynecolOncol. 1989;35:125–7.
2.
Zurück zum Zitat Creasman WT, Morrow CP, Bundy BN, Homesly HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. Cancer. 1987;60:2035–41.CrossRefPubMed Creasman WT, Morrow CP, Bundy BN, Homesly HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. Cancer. 1987;60:2035–41.CrossRefPubMed
3.
Zurück zum Zitat Rubin SC, Hoskins WJ, Saigo PE, Nori D, Mychalczak B, Chapman D, et al. Management of endometrial adenocarcinoma with cervical involvement. Gynecol Oncol. 1992;45:294–8.CrossRefPubMed Rubin SC, Hoskins WJ, Saigo PE, Nori D, Mychalczak B, Chapman D, et al. Management of endometrial adenocarcinoma with cervical involvement. Gynecol Oncol. 1992;45:294–8.CrossRefPubMed
4.
Zurück zum Zitat Morrow CP, Curtin JP, Townsend DG. Tumors of the endometrium. In Synopsis of gynecologic oncology (5th edn), Morrow CP, Curtin JP (eds). Churchill Livingstone: New York, NY, 1998; 151–185. Morrow CP, Curtin JP, Townsend DG. Tumors of the endometrium. In Synopsis of gynecologic oncology (5th edn), Morrow CP, Curtin JP (eds). Churchill Livingstone: New York, NY, 1998; 151–185.
5.
Zurück zum Zitat Kinkel K, Kaji Y, Yu KK, Segal MR, Powell CB, Hricak H. Radiologic staging in patients with endometrial cancer: a metaanalysis. Radiology. 1999;212:711–8.CrossRefPubMed Kinkel K, Kaji Y, Yu KK, Segal MR, Powell CB, Hricak H. Radiologic staging in patients with endometrial cancer: a metaanalysis. Radiology. 1999;212:711–8.CrossRefPubMed
6.
Zurück zum Zitat Ayhan A, Taskiran C, Celik C, Yuce K. The long term survival of women with surgical stage II endometrioid type endometrial cancer. Gynecol Oncol. 2004;93:9–13.CrossRefPubMed Ayhan A, Taskiran C, Celik C, Yuce K. The long term survival of women with surgical stage II endometrioid type endometrial cancer. Gynecol Oncol. 2004;93:9–13.CrossRefPubMed
7.
Zurück zum Zitat Nagar H, Dobbs S, McClelland HR, Price J, McCluggage WG, Grey A. The diagnostic accuracy of magnetic resonance imaging in detecting cervical involvement in endometrial cancer. Gynecol Oncol. 2006;103:431–4.CrossRefPubMed Nagar H, Dobbs S, McClelland HR, Price J, McCluggage WG, Grey A. The diagnostic accuracy of magnetic resonance imaging in detecting cervical involvement in endometrial cancer. Gynecol Oncol. 2006;103:431–4.CrossRefPubMed
8.
Zurück zum Zitat Magrina JF. Outcomes of laparoscopic treatment for endometrial cancer. Curr Opin Obstet Gynecol. 2005;17:343–6.CrossRefPubMed Magrina JF. Outcomes of laparoscopic treatment for endometrial cancer. Curr Opin Obstet Gynecol. 2005;17:343–6.CrossRefPubMed
9.
Zurück zum Zitat Varpula MJ, Klemi PJ. Staging of uterine endometrial carcinoma with ultra-low field (0.02 T) MRI: a comparative study with CT. J Comput Assist Tomogr. 1993;17:641–7.CrossRefPubMed Varpula MJ, Klemi PJ. Staging of uterine endometrial carcinoma with ultra-low field (0.02 T) MRI: a comparative study with CT. J Comput Assist Tomogr. 1993;17:641–7.CrossRefPubMed
10.
Zurück zum Zitat Karlsson B, Norstrom A, Granberg S, Wikland M. The use of endovaginal ultrasound to diagnose invasion of endometrial carcinoma. Ultrasound Obstet Gynecol. 1992;2:35–9.CrossRefPubMed Karlsson B, Norstrom A, Granberg S, Wikland M. The use of endovaginal ultrasound to diagnose invasion of endometrial carcinoma. Ultrasound Obstet Gynecol. 1992;2:35–9.CrossRefPubMed
11.
Zurück zum Zitat Kim SH, Kim HD, Song YS, Kang SB, Lee HP. Detection of deep myometrial invasion in endometrial carcinoma: comparison of transvaginal ultrasound, CT, and MRI. J Comput Assist Tomogr. 1995;19:766–72.CrossRefPubMed Kim SH, Kim HD, Song YS, Kang SB, Lee HP. Detection of deep myometrial invasion in endometrial carcinoma: comparison of transvaginal ultrasound, CT, and MRI. J Comput Assist Tomogr. 1995;19:766–72.CrossRefPubMed
12.
Zurück zum Zitat Hasami K, Matsuzawa M, Chen HF, Takahashi M, Sakura M. Computed tomography in the evaluation and treatment of endometrial carcinoma. Cancer. 1982;50:904–8.CrossRef Hasami K, Matsuzawa M, Chen HF, Takahashi M, Sakura M. Computed tomography in the evaluation and treatment of endometrial carcinoma. Cancer. 1982;50:904–8.CrossRef
13.
Zurück zum Zitat Teefey SA, Stahl JA, Middleton WD, Huettner PC, Bernhard LM, Brown JJ, et al. Local staging of endometrial carcinoma: comparison of transvaginal and intraoperative sonography and gross visual inspection. AJR Am J Roentgenol. 1996;166:547–52.CrossRefPubMed Teefey SA, Stahl JA, Middleton WD, Huettner PC, Bernhard LM, Brown JJ, et al. Local staging of endometrial carcinoma: comparison of transvaginal and intraoperative sonography and gross visual inspection. AJR Am J Roentgenol. 1996;166:547–52.CrossRefPubMed
14.
Zurück zum Zitat Joja I, Asakawa M, Asakawa T, Nakagawa T, Kanazawa S, Kuroda M, et al. Endometrial carcinoma: dynamic MRI with turbo-flash technique. J Comput Assist Tomogr. 1996;20:878–87.CrossRefPubMed Joja I, Asakawa M, Asakawa T, Nakagawa T, Kanazawa S, Kuroda M, et al. Endometrial carcinoma: dynamic MRI with turbo-flash technique. J Comput Assist Tomogr. 1996;20:878–87.CrossRefPubMed
15.
Zurück zum Zitat Seki H, Kimura M, Sakai K. Myometrial invasion of endometrial carcinoma: assessment with plain and gadolinium enhanced MR imaging. Radiology. 1992;185:207–12.CrossRef Seki H, Kimura M, Sakai K. Myometrial invasion of endometrial carcinoma: assessment with plain and gadolinium enhanced MR imaging. Radiology. 1992;185:207–12.CrossRef
16.
Zurück zum Zitat Arko D, Takac I. High frequency transvaginal ultrasonography in preoperative assessment of myometrial invasion in endometrial cancer. J Ultrasound Med. 2000;19:639–43.CrossRefPubMed Arko D, Takac I. High frequency transvaginal ultrasonography in preoperative assessment of myometrial invasion in endometrial cancer. J Ultrasound Med. 2000;19:639–43.CrossRefPubMed
17.
Zurück zum Zitat Manfredi R, Mirk P, Maresca G, Margariti PA, Testa A, Zannoni GF, et al. Local–regional staging of endometrial carcinoma: role of MR imaging in surgical planning. Radiology. 2004;231:372–8.CrossRefPubMed Manfredi R, Mirk P, Maresca G, Margariti PA, Testa A, Zannoni GF, et al. Local–regional staging of endometrial carcinoma: role of MR imaging in surgical planning. Radiology. 2004;231:372–8.CrossRefPubMed
18.
Zurück zum Zitat De Smet F, De Brabanter J, Van den Bosch T, Pochet N, Amant F, Van Holsbeke C, et al. New models to predict depth of infiltration in endometrial carcinoma based on transvaginal sonography. Ultrasound Obstet Gynecol. 2006;27:664–971.CrossRefPubMed De Smet F, De Brabanter J, Van den Bosch T, Pochet N, Amant F, Van Holsbeke C, et al. New models to predict depth of infiltration in endometrial carcinoma based on transvaginal sonography. Ultrasound Obstet Gynecol. 2006;27:664–971.CrossRefPubMed
19.
Zurück zum Zitat Hardesty LA, Sumkin JH, Hakim C, Johns C, Nath M. The ability of helical CT to preoperatively stage endometrial carcinoma. AJR Am J Roentgenol. 2001;176:603–6.CrossRefPubMed Hardesty LA, Sumkin JH, Hakim C, Johns C, Nath M. The ability of helical CT to preoperatively stage endometrial carcinoma. AJR Am J Roentgenol. 2001;176:603–6.CrossRefPubMed
20.
Zurück zum Zitat Savelli L, Ceccarini M, Ludovisi M, Fruscella E, de Laco PA, Salizzoni E, et al. Preoperative local staging of endometrial cancer: transvaginal sonography vs. magnetic resonance imaging. Ultrasound Obstet Gynecol. 2008;31:560–6.CrossRefPubMed Savelli L, Ceccarini M, Ludovisi M, Fruscella E, de Laco PA, Salizzoni E, et al. Preoperative local staging of endometrial cancer: transvaginal sonography vs. magnetic resonance imaging. Ultrasound Obstet Gynecol. 2008;31:560–6.CrossRefPubMed
21.
Zurück zum Zitat Scambia G, Benedetti Panici P, Baiocchi G, Perrone L, Greggi S, Mancuso S. CA 15–3 as a tumor marker in gynecological malignancies. Gynecol Oncol. 1988;30(2):265–73.CrossRefPubMed Scambia G, Benedetti Panici P, Baiocchi G, Perrone L, Greggi S, Mancuso S. CA 15–3 as a tumor marker in gynecological malignancies. Gynecol Oncol. 1988;30(2):265–73.CrossRefPubMed
22.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat 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;104:1418–25.CrossRefPubMedPubMedCentral 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;104:1418–25.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat 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 ovarian carcinomas. Cancer Res. 2005;65(6):2162–9.CrossRefPubMed 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 ovarian carcinomas. Cancer Res. 2005;65(6):2162–9.CrossRefPubMed
25.
Zurück zum Zitat Kobel M, Kalloger SE, Boyd N, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med. 2008;5(12):e232.CrossRefPubMedPubMedCentral Kobel M, Kalloger SE, Boyd N, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med. 2008;5(12):e232.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Plotti F, Capriglione S, Terranova C, Montera R, Aloisi A, Damiani P, et al. Does HE4 have a role as biomarker in the recurrence of ovarian cancer? Tumour Biol. 2012;33(6):2117–23.CrossRefPubMed Plotti F, Capriglione S, Terranova C, Montera R, Aloisi A, Damiani P, et al. Does HE4 have a role as biomarker in the recurrence of ovarian cancer? Tumour Biol. 2012;33(6):2117–23.CrossRefPubMed
27.
Zurück zum Zitat Angioli R, Miranda A, Aloisi A, Montera R, Capriglione S, De Cicco NC, et al. A critical review on HE4 performance in endometrial cancer: where are we now? Tumour Biol. 2014;35(2):881–7.CrossRefPubMed Angioli R, Miranda A, Aloisi A, Montera R, Capriglione S, De Cicco NC, et al. A critical review on HE4 performance in endometrial cancer: where are we now? Tumour Biol. 2014;35(2):881–7.CrossRefPubMed
28.
Zurück zum Zitat Duk IM. CA125: a useful marker in endometrial carcinoma. Am J Obstet Gynaecol Oncol. 1994;54(3):321–6. Duk IM. CA125: a useful marker in endometrial carcinoma. Am J Obstet Gynaecol Oncol. 1994;54(3):321–6.
29.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
30.
Zurück zum Zitat Angioli R, Capriglione S, Aloisi A, Luvero D, Cafà EV, Dugo N, et al. REM (risk of endometrial malignancy): a proposal for a new scoring system to evaluate risk of endometrial malignancy. Clin Cancer Res. 2013;19(20):5733–9.CrossRefPubMed Angioli R, Capriglione S, Aloisi A, Luvero D, Cafà EV, Dugo N, et al. REM (risk of endometrial malignancy): a proposal for a new scoring system to evaluate risk of endometrial malignancy. Clin Cancer Res. 2013;19(20):5733–9.CrossRefPubMed
31.
Zurück zum Zitat Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet. 2005;366(9484):491–505.CrossRefPubMed Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet. 2005;366(9484):491–505.CrossRefPubMed
32.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
33.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
34.
Zurück zum Zitat Zanotti L, Bignotti E, Calza S, Bandiera E, Ruggeri G, Galli C, et al. Human epididymis protein 4 as a serum for diagnosis of endometrial carcinoma and prediction of clinical out come. Clin Chem Lab Med. 2012;50(12):2189–98.CrossRefPubMed Zanotti L, Bignotti E, Calza S, Bandiera E, Ruggeri G, Galli C, et al. Human epididymis protein 4 as a serum for diagnosis of endometrial carcinoma and prediction of clinical out come. Clin Chem Lab Med. 2012;50(12):2189–98.CrossRefPubMed
35.
Zurück zum Zitat 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–el-6.CrossRefPubMed 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–el-6.CrossRefPubMed
36.
Zurück zum Zitat Omer B, Genc S, Takmaz O, Dirican A, Kusku-Kiraz Z, Berkman S, et al. The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients. Tumor Biol. 2013;34(5):2645–50.CrossRef Omer B, Genc S, Takmaz O, Dirican A, Kusku-Kiraz Z, Berkman S, et al. The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients. Tumor Biol. 2013;34(5):2645–50.CrossRef
37.
Zurück zum Zitat 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
Metadaten
Titel
Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study
verfasst von
Stella Capriglione
Francesco Plotti
Andrea Miranda
Roberto Ricciardi
Giuseppe Scaletta
Alessia Aloisi
Federica Guzzo
Roberto Montera
Roberto Angioli
Publikationsdatum
01.06.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 6/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3049-3

Weitere Artikel der Ausgabe 6/2015

Tumor Biology 6/2015 Zur Ausgabe

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.