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Erschienen in: Tumor Biology 4/2016

03.11.2015 | Original Article

The role of HE4 in endometrial cancer recurrence: how to choose the optimal follow-up program

verfasst von: Roberto Angioli, Stella Capriglione, Giuseppe Scaletta, Alessia Aloisi, Andrea Miranda, Carlo De Cicco Nardone, Corrado Terranova, Francesco Plotti

Erschienen in: Tumor Biology | Ausgabe 4/2016

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Abstract

The aim of this study was to evaluate for the first time in the literature the role of HE4, at primary diagnosis, compared to CA125 as an indicator of endometrial cancer (EC) recurrence. Our study is a retrospective analysis of 252 EC patients treated, between January 2009 and July 2013, at the Division of Gynaecologic Oncology of Campus Bio-Medico University of Rome. Thirty-seven patients experienced recurrence. Median follow-up was 38 months. HE4 and CA125 levels were analyzed at primary diagnosis, during follow-up and either after histological or radiological confirmation of recurrent disease or at last registered visit, when patients returned to our Department with no evidence of recurrent disease. A statistically significant difference was observed between HE4 values at primary diagnosis and at recurrence, respectively, comparing recurrent and non-recurrent patients (p < 0.05), while CA125 values resulted not statistically significant (p = 0.08) at each time point. Considering the poor specificity of HE4 at threshold of 70 pmol/L at primary diagnosis, in our cohort of patients, we found out that HE4 cut-off of 201.3 pmol/L is able to correctly classify patients at high or low risk of EC recurrence, with a sensitivity of 80 % and a specificity of 91 % (PPV = 90.3 % and NPV = 90.8 %). In particular, HE4 performance improves in cases of endometrioid histotype. HE4 levels at primary diagnosis correlate with an increased risk of EC recurrence, particularly in cases of endometrioid histotype, and they may help to recognize patients who may need a more intensive follow-up.
Literatur
1.
Zurück zum Zitat Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon: International Agency for Research on Cancer; 2013. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon: International Agency for Research on Cancer; 2013.
2.
Zurück zum Zitat 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;198:218.e211–6.CrossRef 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;198:218.e211–6.CrossRef
3.
Zurück zum Zitat Fung-Kee-Fung M, Dodge J, Elit L, Lukka H, Chambers A, Oliver T, et al. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. 2006;101(3):520–9.CrossRefPubMed Fung-Kee-Fung M, Dodge J, Elit L, Lukka H, Chambers A, Oliver T, et al. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. 2006;101(3):520–9.CrossRefPubMed
4.
Zurück zum Zitat Smith CJ, Heeren M, Nicklin JL, Perrin LC, Land R, Crandon AJ, et al. Efficacy of routine follow-up in patients with recurrent uterine cancer. Gynecol Oncol. 2007;107(1):124–9.CrossRefPubMed Smith CJ, Heeren M, Nicklin JL, Perrin LC, Land R, Crandon AJ, et al. Efficacy of routine follow-up in patients with recurrent uterine cancer. Gynecol Oncol. 2007;107(1):124–9.CrossRefPubMed
5.
Zurück zum Zitat Salani R, Backes FJ, Fung MF, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol. 2011;204:466–78.CrossRefPubMed Salani R, Backes FJ, Fung MF, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol. 2011;204:466–78.CrossRefPubMed
6.
Zurück zum Zitat Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C, Sessa C; ESMO Guidelines Working Group. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi33–8. Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C, Sessa C; ESMO Guidelines Working Group. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi33–8.
7.
Zurück zum Zitat Aggarwal P, Kehoe S. Serum tumour markers in gynaecological cancers. Maturitas. 2010;67:46–53.CrossRefPubMed Aggarwal P, Kehoe S. Serum tumour markers in gynaecological cancers. Maturitas. 2010;67:46–53.CrossRefPubMed
8.
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(9):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(9):1418–25.CrossRefPubMedPubMedCentral
9.
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
10.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
11.
Zurück zum Zitat Capriglione S, Plotti F, Miranda A, Ricciardi R, Scaletta G, Aloisi A, et al. Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study. Tumour Biol. 2015;36(6):4151–6.CrossRefPubMed Capriglione S, Plotti F, Miranda A, Ricciardi R, Scaletta G, Aloisi A, et al. Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study. Tumour Biol. 2015;36(6):4151–6.CrossRefPubMed
12.
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
13.
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
14.
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
15.
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
16.
Zurück zum Zitat Brennan DJ, Hackethal A, Metcalf AM, Coward J, Ferguson K, Oehler MK, et al. Serum HE4 as a prognostic marker in endometrial cancer—a population based study. Gynecol Oncol. 2014;132(1):159–65.CrossRefPubMed Brennan DJ, Hackethal A, Metcalf AM, Coward J, Ferguson K, Oehler MK, et al. Serum HE4 as a prognostic marker in endometrial cancer—a population based study. Gynecol Oncol. 2014;132(1):159–65.CrossRefPubMed
17.
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
18.
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
19.
Zurück zum Zitat Brennan DJ, Hackethal A, Mann KP, Mutz-Dehbalaie I, Fiegl H, Marth C, et al. Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance. BMC Cancer. 2015;15:33.CrossRefPubMedPubMedCentral Brennan DJ, Hackethal A, Mann KP, Mutz-Dehbalaie I, Fiegl H, Marth C, et al. Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance. BMC Cancer. 2015;15:33.CrossRefPubMedPubMedCentral
20.
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
21.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRef Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRef
22.
Zurück zum Zitat Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003;89(2):201–9.CrossRefPubMed Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003;89(2):201–9.CrossRefPubMed
23.
Zurück zum Zitat Lajer H, Jensen MB, Kilsmark J, Albaek J, Svane D, Mirza MR, et al. The value of gynecologic cancer follow-up: evidence-based ignorance? Int J Gynecol Cancer. 2010;20:1307–20.PubMed Lajer H, Jensen MB, Kilsmark J, Albaek J, Svane D, Mirza MR, et al. The value of gynecologic cancer follow-up: evidence-based ignorance? Int J Gynecol Cancer. 2010;20:1307–20.PubMed
24.
Zurück zum Zitat Zanagnolo V, Ming L, Gadducci A, Maggino T, Sartori E, Zola P, et al. Surveillance procedures for patients with cervical carcinoma: a review of the literature. Int J Gynecol Cancer. 2009;19:194–201.CrossRefPubMed Zanagnolo V, Ming L, Gadducci A, Maggino T, Sartori E, Zola P, et al. Surveillance procedures for patients with cervical carcinoma: a review of the literature. Int J Gynecol Cancer. 2009;19:194–201.CrossRefPubMed
25.
Zurück zum Zitat Sartori E, Pasinetti B, Chiudinelli F, Gadducci A, Landoni F, Maggino T, et al. Surveillance procedures for patients treated for endometrial cancer: a review of the literature. Int J Gynecol Cancer. 2010;20:985–92.CrossRefPubMed Sartori E, Pasinetti B, Chiudinelli F, Gadducci A, Landoni F, Maggino T, et al. Surveillance procedures for patients treated for endometrial cancer: a review of the literature. Int J Gynecol Cancer. 2010;20:985–92.CrossRefPubMed
26.
Zurück zum Zitat Lo SS, Khoo US, Cheng DK, Ng TY, Wong LC, Ngan HY. Role of serial tumor markers in the surveillance for recurrence in endometrial cancer. Cancer Detect Prev. 1999;23(5):397–400.CrossRefPubMed Lo SS, Khoo US, Cheng DK, Ng TY, Wong LC, Ngan HY. Role of serial tumor markers in the surveillance for recurrence in endometrial cancer. Cancer Detect Prev. 1999;23(5):397–400.CrossRefPubMed
27.
Zurück zum Zitat Patsner B, Orr Jr JW, Mann Jr WJ. Use of serum CA 125 measurement in posttreatment surveillance of early-stage endometrial carcinoma. Am J Obstet Gynecol. 1990;162(2):427–9.CrossRefPubMed Patsner B, Orr Jr JW, Mann Jr WJ. Use of serum CA 125 measurement in posttreatment surveillance of early-stage endometrial carcinoma. Am J Obstet Gynecol. 1990;162(2):427–9.CrossRefPubMed
28.
Zurück zum Zitat Rose PG, Sommers RM, Reale FR, Hunter RE, Fournier L, Nelson BE. Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma. Obstet Gynecol. 1994;84(1):12–6.PubMed Rose PG, Sommers RM, Reale FR, Hunter RE, Fournier L, Nelson BE. Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma. Obstet Gynecol. 1994;84(1):12–6.PubMed
29.
Zurück zum Zitat Lv YW, Yang L, Zhang M, Jiang LH, Niu JH, Hou J, et al. Increased human epididymis protein 4 in benign gynecological diseases complicated with chronic renal insufficiency patients. Genet Mol Res. 2015;14(1):2156–61.CrossRefPubMed Lv YW, Yang L, Zhang M, Jiang LH, Niu JH, Hou J, et al. Increased human epididymis protein 4 in benign gynecological diseases complicated with chronic renal insufficiency patients. Genet Mol Res. 2015;14(1):2156–61.CrossRefPubMed
Metadaten
Titel
The role of HE4 in endometrial cancer recurrence: how to choose the optimal follow-up program
verfasst von
Roberto Angioli
Stella Capriglione
Giuseppe Scaletta
Alessia Aloisi
Andrea Miranda
Carlo De Cicco Nardone
Corrado Terranova
Francesco Plotti
Publikationsdatum
03.11.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4324-z

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