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Serum Levels of CA125 and HE4 as a Tool for Predicting Regional Lymph Node Metastatic Involvement in Endometrial Carcinoma

. 2025 Aug 23 ; 17 (17) : . [epub] 20250823

Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic

Document type Journal Article

Background: Endometrial carcinoma is the most common gynaecological malignant tumour in developed countries. At present, no routinely used serum biomarker is available for the prediction of lymph node metastasis (LNM). This study thus evaluates the potential of tumour markers CA125 and HE4 as LNM predictors in endometrial carcinoma patients. Objectives: The aim of this study was to evaluate the potential use of CA125 and HE4 and to assess the viability of a model developed using the parameters of serum tumour marker levels for LNM risk stratification. Methods: A retrospective, single-institution study of 220 patients with biopsy-proven endometrial carcinoma was conducted from May 2020 to December 2023. Preoperative serum levels of HE4 and CA125 were determined. All patients underwent surgical lymph node staging. The study evaluated the sensitivity and specificity of tumour markers and of the developed LNM risk prediction model. Results: No LNM was observed in 167 of the 220 patients (75.9%), micrometastatic lymph node involvement was observed in 13 patients (5.9%), and macrometastatic involvement was observed in 24 patients (10.9%). Median CA125 and HE4 levels were significantly higher in patients with LNM than in those without. With a CA125 cut-off value of 35 IU/mL, a sensitivity of 70% and a specificity of 92% were obtained, while an HE4 cut-off value of 103 pmol/L yielded a sensitivity of 78% and a specificity of 80%. A prediction model combining CA125, HE4, and the extent of uterine invasion, as detected by ultrasound, yielded a sensitivity of 84% and a specificity of 98% in predicting LNM. Conclusions: CA125 and HE4, along with the prediction model, facilitate endometrial carcinoma patient subdivision into low- and high-risk LNM groups. As this method is technically simple, non-invasive, and inexpensive, it could be of undeniable benefit in the risk stratification of patients with multiple comorbidities, which limit the duration and extent of surgery.

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Ferlay J., Ervik M., Lam F., Laversanne M., Colombet M., Mery L., Piñeros M., Znaor A., Soerjomataram I., Bray F. Global Cancer Observatory: Cancer Today. International Agency for Research on Cancer; Lyon, France: 2024. [(accessed on 5 May 2025)]. Available online: https://gco.iarc.who.int/today.

World Health Organization . GLOBOCAN 2018: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2018. World Health Organization; Geneva, Switzerland: 2018. [(accessed on 29 July 2020)]. Available online: https://gco.iarc.who.int/media/globocan/factsheets/cancers/24-corpus-uteri-fact-sheet.pdf.

Clarke M.A., Long B.J., Del Mar Morillo A., Arbyn M., Bakkum-Gamez J.N., Wentzensen N. Association of Endometrial Cancer Risk with Postmenopausal Bleeding in Women: A Systematic Review and Meta-Analysis. JAMA Intern. Med. 2018;178:1210–1222. doi: 10.1001/jamainternmed.2018.2820. PubMed DOI PMC

National Cancer Institute . Endometrial Cancer Treatment (PDQ®)–Patient Version [Internet] National Cancer Institute; Bethesda, MD, USA: 2019. [(accessed on 19 December 2019)]. Available online: https://www.cancer.gov/types/uterine/patient/endometrial-treatment-pdq.

Concin N., Matias-Guiu X., Cibula D., Colombo N., Creutzberg C.L., Ledermann J., Mirza M.R., Vergote I., Abu-Rustum N.R., Bosse T., et al. ESGO-ESTRO-ESP Guidelines for the Management of Patients with Endometrial Carcinoma: Update 2025. Lancet Oncol. 2025;26:e423–e435. doi: 10.1016/S1470-2045(25)00167-6. PubMed DOI

Accorsi G.S., Paiva L.L., Schmidt R., Vieira M., Reis R., Andrade C. Sentinel Lymph Node Mapping vs Systematic Lymphadenectomy for Endometrial Cancer: Surgical Morbidity and Lymphatic Complications. J. Minim. Invasive Gynecol. 2020;27:938–945.e2. doi: 10.1016/j.jmig.2019.07.030. PubMed DOI

Bogani G., Dowdy S.C., Cliby W.A., Ghezzi F., Rossetti D., Mariani A. Role of Pelvic and Para-Aortic Lymphadenectomy in Endometrial Cancer: Current Evidence. J. Obstet. Gynaecol. Res. 2014;40:301–311. doi: 10.1111/jog.12344. PubMed DOI PMC

Daoud T., Sardana S., Stanietzky N., Klekers A.R., Bhosale P., Morani A.C. Recent Imaging Updates and Advances in Gynecologic Malignancies. Cancers. 2022;14:5528. doi: 10.3390/cancers14225528. PubMed DOI PMC

Haldorsen I.S., Salvesen H.B. What Is the Best Preoperative Imaging for Endometrial Cancer? Curr. Oncol. Rep. 2016;18:25. doi: 10.1007/s11912-016-0506-0. PubMed DOI PMC

Lin Y., Dobrotwir A., McNally O., Abu-Rustum N.R., Narayan K. Role of Imaging in the Routine Management of Endometrial Cancer. Int. J. Gynecol. Obstet. 2018;143:109–117. doi: 10.1002/ijgo.12618. PubMed DOI PMC

Epstein E., Blomqvist L. Imaging in Endometrial Cancer. Best. Pract. Res. Clin. Obstet. Gynaecol. 2014;28:721–739. doi: 10.1016/j.bpobgyn.2014.04.007. PubMed DOI

Bast R.C., Feeney M., Lazarus H., Nadler L.M., Colvin R.B., Knapp R.C. Reactivity of a Monoclonal Antibody with Human Ovarian Carcinoma. J. Clin. Investig. 1981;68:1331–1337. doi: 10.1172/JCI110380. PubMed DOI PMC

Qu W., Gao Q., Chen H., Tang Z., Zhu X., Jiang S.-W. HE4-Test of Urine and Body Fluids for Diagnosis of Gynecologic Cancer. Expert. Rev. Mol. Diagn. 2017;17:239–244. doi: 10.1080/14737159.2017.1282824. PubMed DOI

Galgano M.T., Hampton G.M., Frierson H.F. Comprehensive Analysis of HE4 Expression in Normal and Malignant Human Tissues. Mod. Pathol. 2006;19:847–853. doi: 10.1038/modpathol.3800612. PubMed DOI

Antonsen S.L., Høgdall E., Christensen I.J., Lydolph M., Tabor A., Loft Jakobsen A., Fagö-Olsen C.L., Andersen E.S., Jochumsen K., Høgdall C. HE4 and CA125 Levels in the Preoperative Assessment of Endometrial Cancer Patients: A Prospective Multicenter Study (ENDOMET) Acta Obstet. Gynecol. Scand. 2013;92:1313–1322. doi: 10.1111/aogs.12235. PubMed DOI

Reijnen C., IntHout J., Massuger L.F.A.G., Strobbe F., Küsters-Vandevelde H.V.N., Haldorsen I.S., Snijders M.P.L.M., Pijnenborg J.M.A. Diagnostic Accuracy of Clinical Biomarkers for Preoperative Prediction of Lymph Node Metastasis in Endometrial Carcinoma: A Systematic Review and Meta-Analysis. Oncologist. 2019;24:e880–e890. doi: 10.1634/theoncologist.2019-0117. PubMed DOI PMC

Behrouzi R., Barr C.E., Crosbie E.J. HE4 as a Biomarker for Endometrial Cancer. Cancers. 2021;13:4764. doi: 10.3390/cancers13194764. PubMed DOI PMC

Lombaers M.S., Cornel K.M.C., Visser N.C.M., Bulten J., Küsters-Vandevelde H.V.N., Amant F., Boll D., Bronsert P., Colas E., Geomini P.M.A.J., et al. Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer. Cancers. 2023;15:2605. doi: 10.3390/cancers15092605. PubMed DOI PMC

Barr C.E., Njoku K., Jones E.R., Crosbie E.J. Serum CA125 and HE4 as Biomarkers for the Detection of Endometrial Cancer and Associated High-Risk Features. Diagnostics. 2022;12:2834. doi: 10.3390/diagnostics12112834. PubMed DOI PMC

Wang Y., Han C., Teng F., Bai Z., Tian W., Xue F. Predictive Value of Serum HE4 and CA125 Concentrations for Lymphatic Metastasis of Endometrial Cancer. Int. J. Gynaecol. Obstet. 2017;136:58–63. doi: 10.1002/ijgo.12010. PubMed DOI

O’Toole S.A., Huang Y., Norris L., Power Foley M., Shireen R., McDonald S., Kamran W., Ibrahim N., Ward M., Thompson C., et al. HE4 and CA125 as Preoperative Risk Stratifiers for Lymph Node Metastasis in Endometrioid Carcinoma of the Endometrium: A Retrospective Study in a Cohort with Histological Proof of Lymph Node Status. Gynecol. Oncol. 2021;160:514–519. doi: 10.1016/j.ygyno.2020.11.004. PubMed DOI

Chung H.H., Kim J.W., Park N.-H., Song Y.-S., Kang S.-B., Lee H.-P. Use of Preoperative Serum CA-125 Levels for Prediction of Lymph Node Metastasis and Prognosis in Endometrial Cancer. Acta Obstet. Gynecol. Scand. 2006;85:1501–1505. doi: 10.1080/00016340601022777. PubMed DOI

Abdalla N., Pazura M., Słomka A., Piórkowski R., Sawicki W., Cendrowski K. The role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies. Ginekol. Pol. 2016;87:781–786. doi: 10.5603/GP.2016.0088. PubMed DOI

Creasman W. Revised FIGO Staging for Carcinoma of the Endometrium. Int. J. Gynecol. Obstet. 2009;105:109. doi: 10.1016/j.ijgo.2009.02.010. PubMed DOI

Amin M.B., Greene F.L., Edge S.B., Compton C.C., Gershenwald J.E., Brookland R.K., Meyer L., Gress D.M., Byrd D.R., Winchester D.P. The Eighth Edition AJCC Cancer Staging Manual: Continuing to Build a Bridge from a Population-Based to a More “Personalized” Approach to Cancer Staging. CA Cancer J. Clin. 2017;67:93–99. doi: 10.3322/caac.21388. PubMed DOI

Plotti F., Scaletta G., Terranova C., Montera R., De Cicco Nardone C., Luvero D., Rossini G., Gatti A., Schirò T., Moncelli M., et al. The Role of Human Epididymis Protein 4 as a Biomarker in Gynecologic Malignancies. Minerva Ginecol. 2019;71:36–43. doi: 10.23736/S0026-4784.18.04328-9. PubMed DOI

Powell J.L., Hill K.A., Shiro B.C., Diehl S.J., Gajewski W.H. Preoperative Serum CA-125 Levels in Treating Endometrial Cancer. J. Reprod. Med. 2005;50:585–590. PubMed

Ginath S., Menczer J., Fintsi Y., Ben-Shem E., Glezerman M., Avinoach I. Tissue and Serum CA125 Expression in Endometrial Cancer. Int. J. Gynecol. Cancer. 2002;12:372–375. doi: 10.1136/ijgc-00009577-200207000-00007. PubMed DOI

Capozzi V.A., Sozzi G., Rosati A., Restaino S., Gambino G., Cianciolo A., Ceccaroni M., Uccella S., Franchi M., Chiantera V., et al. Predictive Score of Nodal Involvement in Endometrial Cancer Patients: A Large Multicentre Series. Ann. Surg. Oncol. 2022;29:2594–2599. doi: 10.1245/s10434-021-11083-x. PubMed DOI

Shawn LyBarger K., Miller H.A., Frieboes H.B. CA125 as a Predictor of Endometrial Cancer Lymphovascular Space Invasion and Lymph Node Metastasis for Risk Stratification in the Preoperative Setting. Sci. Rep. 2022;12:19783. doi: 10.1038/s41598-022-22026-1. PubMed DOI PMC

Ünsal M., Kimyon Comert G., Karalok A., Basaran D., Turkmen O., Boyraz G., Tasci T., Koc S., Boran N., Tulunay G., et al. The Preoperative Serum CA125 Can Predict the Lymph Node Metastasis in Endometrioid-Type Endometrial Cancer. Ginekol. Pol. 2018;89:599–606. doi: 10.5603/GP.a2018.0103. PubMed DOI

Frühauf F., Dvořák M., Haaková L., Hašlík L., Herboltová P., Chaloupková B., Kožnarová J., Kubešová B., Lukáčová I., Marek R. Ultrasound staging of endometrial cancer—Recommended methodology of examination. Ceska Gynekol. 2014;79:466–476. PubMed

Christensen J.W., Dueholm M., Hansen E.S., Marinovskij E., Lundorf E., Ørtoft G. Assessment of Myometrial Invasion in Endometrial Cancer Using Three-Dimensional Ultrasound and Magnetic Resonance Imaging. Acta Obstet. Gynecol. Scand. 2016;95:55–64. doi: 10.1111/aogs.12806. PubMed DOI

Jantarasaengaram S., Praditphol N., Tansathit T., Vipupinyo C., Vairojanavong K. Three-Dimensional Ultrasound with Volume Contrast Imaging for Preoperative Assessment of Myometrial Invasion and Cervical Involvement in Women with Endometrial Cancer. Ultrasound Obstet. Gynecol. 2014;43:569–574. doi: 10.1002/uog.13200. PubMed DOI

Fischerova D., Smet C., Scovazzi U., Sousa D.N., Hundarova K., Haldorsen I.S. Staging by Imaging in Gynecologic Cancer and the Role of Ultrasound: An Update of European Joint Consensus Statements. Int. J. Gynecol. Cancer. 2024;34:363–378. doi: 10.1136/ijgc-2023-004609. PubMed DOI PMC

Kim H.J., Cho A., Yun M., Kim Y.T., Kang W.J. Comparison of FDG PET/CT and MRI in Lymph Node Staging of Endometrial Cancer. Ann. Nucl. Med. 2016;30:104–113. doi: 10.1007/s12149-015-1037-8. PubMed DOI

Bollineni V.R., Ytre-Hauge S., Bollineni-Balabay O., Salvesen H.B., Haldorsen I.S. High Diagnostic Value of 18F-FDG PET/CT in Endometrial Cancer: Systematic Review and Meta-Analysis of the Literature. J. Nucl. Med. 2016;57:879–885. doi: 10.2967/jnumed.115.170597. PubMed DOI

Tanaka T., Terai Y., Yamamoto K., Yamada T., Ohmichi M. The Diagnostic Accuracy of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography and Sentinel Node Biopsy in the Prediction of Pelvic Lymph Node Metastasis in Patients with Endometrial Cancer: A Retrospective Observational Study. Medicine. 2018;97:e12522. doi: 10.1097/MD.0000000000012522. PubMed DOI PMC

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