---
title: "Urinary biomarkers for endometrial cancer detection: advances and clinical potential"
id: "british-journal-of-cancer-0-advances-in-urinary-biomarkers-for-endometrial-cancer-detection"
canonical_url: "https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-advances-in-urinary-biomarkers-for-endometrial-cancer-detection"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "British Journal of Cancer"
source_url: "https://www.nature.com/articles/s41416-026-03579-8"
published_at: "2026-08-11T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Urinary biomarkers for endometrial cancer detection: advances and clinical potential
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-advances-in-urinary-biomarkers-for-endometrial-cancer-detection
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** British Journal of Cancer
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41416-026-03579-8)
- **Published At:** 2026-08-11T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The incidence of **endometrial cancer** is rising globally, driven by ageing and increasing obesity; over 420,000 new cases and ~98,000 deaths were reported in 2022. Diagnostic workloads are increasing while most symptomatic women do not have cancer. - Current evaluation of abnormal uterine bleeding relies on **transvaginal ultrasound** (TVUS) followed by invasive endometrial visualisation and sampling. These pathways are resource intensive and often unnecessary for the majority of symptomatic women. - **Urine** is a non-invasive, repeatable biofluid that can capture tumour-associated signals via renal filtration of systemic markers and through locally shed uterine material, supporting its investigation as a diagnostic medium. - Emerging urinary biomarker classes include somatic mutation assays, **DNA methylation** panels, proteins and peptides, vibrational spectroscopy signatures, microRNAs, metabolites, and **urine cytology**. - Biomarkers reflect biological processes in endometrial carcinogenesis: hormonal and metabolic dysregulation, immune activation, epithelial–stromal disruption, proliferation, and genomic instability. - Some mutation-based assays and **DNA methylation** panels have reported sensitivities and specificities exceeding 80–90% in symptomatic cohorts; **urine cytology** also shows potential in selected populations. - Proteomic, metabolomic and spectroscopy approaches are promising but need further standardisation, larger prospective validation and reproducible protocols. - Urinary biomarkers are not yet ready for population screening but could be useful for risk stratification and triage of symptomatic women to reduce unnecessary invasive tests. - Clinical translation will require standardised pre-analytical protocols, multi-centre validation studies, and integration into existing diagnostic pathways such as TVUS and endometrial sampling. - The review highlights the potential and the remaining evidence gaps rather than definitive clinical recommendations; details on many candidate assays and validation cohorts were not fully reported in the source abstract and introduction provided.
## Clinical Analysis & Structured Key Points
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[nature](https://www.nature.com/) 2. [british journal of cancer](https://www.nature.com/bjc) 3. [review articles](https://www.nature.com/bjc/articles?type=review-article) 4. article Advances in urinary biomarkers for endometrial cancer detection [ Download PDF ](https://www.nature.com/articles/s41416-026-03579-8.pdf) [ Download PDF ](https://www.nature.com/articles/s41416-026-03579-8.pdf) * Review Article * [Open access](https://www.springernature.com/gp/open-science/about/the-fundamentals-of-open-access-and-open-research) * Published: 11 August 2026 Molecular Diagnostics # Advances in urinary biomarkers for endometrial cancer detection * [Molly Dore](https://www.nature.com/articles/s41416-026-03579-8#auth-Molly-Dore-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03579-8#Aff1),[2](https://www.nature.com/articles/s41416-026-03579-8#Aff2) [na1](https://www.nature.com/articles/s41416-026-03579-8#na1), * [Jiexin Cao](https://www.nature.com/articles/s41416-026-03579-8#auth-Jiexin-Cao-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03579-8#Aff1),[2](https://www.nature.com/articles/s41416-026-03579-8#Aff2) [na1](https://www.nature.com/articles/s41416-026-03579-8#na1), * [Holly Baker-Rand](https://www.nature.com/articles/s41416-026-03579-8#auth-Holly-Baker_Rand-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03579-8#Aff1),[2](https://www.nature.com/articles/s41416-026-03579-8#Aff2) [na1](https://www.nature.com/articles/s41416-026-03579-8#na1), * [Ananya Choudhury](https://www.nature.com/articles/s41416-026-03579-8#auth-Ananya-Choudhury-Aff2)[2](https://www.nature.com/articles/s41416-026-03579-8#Aff2), * [Anthony D. Whetton](https://www.nature.com/articles/s41416-026-03579-8#auth-Anthony_D_-Whetton-Aff3)[3](https://www.nature.com/articles/s41416-026-03579-8#Aff3), * [Richard D. Unwin](https://www.nature.com/articles/s41416-026-03579-8#auth-Richard_D_-Unwin-Aff2)[2](https://www.nature.com/articles/s41416-026-03579-8#Aff2), * [Emma J. Davidson](https://www.nature.com/articles/s41416-026-03579-8#auth-Emma_J_-Davidson-Aff1-Aff2-Aff3-Aff4-Aff5) [ORCID: orcid.org/0000-0003-0284-8630](https://orcid.org/0000-0003-0284-8630)[1](https://www.nature.com/articles/s41416-026-03579-8#Aff1),[2](https://www.nature.com/articles/s41416-026-03579-8#Aff2),[3](https://www.nature.com/articles/s41416-026-03579-8#Aff3),[4](https://www.nature.com/articles/s41416-026-03579-8#Aff4),[5](https://www.nature.com/articles/s41416-026-03579-8#Aff5) [na2](https://www.nature.com/articles/s41416-026-03579-8#na2) & * … * [Kelechi Njoku](https://www.nature.com/articles/s41416-026-03579-8#auth-Kelechi-Njoku-Aff1-Aff2-Aff6-Aff7) [ORCID: orcid.org/0000-0001-6528-3476](https://orcid.org/0000-0001-6528-3476)[1](https://www.nature.com/articles/s41416-026-03579-8#Aff1),[2](https://www.nature.com/articles/s41416-026-03579-8#Aff2),[6](https://www.nature.com/articles/s41416-026-03579-8#Aff6),[7](https://www.nature.com/articles/s41416-026-03579-8#Aff7) [na2](https://www.nature.com/articles/s41416-026-03579-8#na2) Show authors [_British Journal of Cancer_](https://www.nature.com/bjc) (2026) [Cite this article](https://www.nature.com/articles/s41416-026-03579-8#citeas) [ Save article ](https://www.nature.com/articles/s41416-026-03579-8/save-research?_csrf=_uIBP3pb2pWxZZJfs_eaFsoMdVxDEQv7) [ View saved research ](https://www.nature.com/saved-research) ## Abstract The incidence of endometrial cancer is rising globally, placing significant burden on diagnostic pathways for women with abnormal uterine bleeding. Current evaluation relies primarily on transvaginal ultrasound followed by invasive endometrial visualisation and sampling, although most symptomatic women have no sinister underlying pathology. Urine offers a promising non-invasive and easily repeatable biofluid capable of capturing tumour-associated signals through both systemic renal filtration and locally shed uterine material. This review summarises emerging evidence on urinary biomarkers for endometrial cancer detection, including somatic mutations, DNA methylation markers, proteins and peptides, vibrational spectroscopy signatures, microRNAs, metabolites and urine cytology. These biomarkers collectively reflect key biological processes driving endometrial carcinogenesis, including hormonal and metabolic dysregulation, immune activation, epithelial–stromal disruption, cellular proliferation and genomic instability. Among current candidates, DNA methylation panels and mutation-based assays have demonstrated encouraging diagnostic performance, with studies reporting sensitivities and specificities exceeding 80–90% in symptomatic populations. Urine cytology also shows strong diagnostic potential in selected cohorts, while metabolomic, proteomic and spectroscopy-based approaches remain promising but require further standardisation and prospective validation. Although not yet suitable for population screening, urinary biomarkers show considerable potential for risk stratification and triage of symptomatic women, potentially reducing unnecessary invasive investigations. Clinical translation will require standardised protocols, multi-centre validation and integration into existing diagnostic pathways. ## Introduction Endometrial cancer is the sixth most common malignancy in women worldwide, with over 420,000 new cases and approximately 98,000 deaths reported in 2022 [[1](https://www.nature.com/articles/s41416-026-03579-8#ref-CR1 "Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63."), [2](https://www.nature.com/articles/s41416-026-03579-8#ref-CR2 "Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399:1412–28.")]. The global age-standardised incidence rate is estimated at 8.4 per 100,000 women, although substantial geographic variation exists [[1](https://www.nature.com/articles/s41416-026-03579-8#ref-CR1 "Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63."), [3](https://www.nature.com/articles/s41416-026-03579-8#ref-CR3 "Makker V, MacKay H, Ray-Coquard I, Levine DA, Westin SN, Aoki D, et al. Endometrial cancer. Nat Rev Dis Prim. 2021;7:88.")]. In the UK, the incidence of endometrial cancer has risen markedly over the past three decades. Cases increased by 59% between 1993 and 2018 and currently more than 10,000 cases are diagnosed annually accounting for approximately 5% of all female cancer diagnoses [[4](https://www.nature.com/articles/s41416-026-03579-8#ref-CR4 "Cancer Research UK. Uterine cancer statistics \[Internet\]. London, United Kingdom: Cancer Research UK; 2024 \[Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/uterine-cancer .")]. The rising incidence of endometrial cancer parallels demographic ageing and the escalating prevalence of obesity. Approximately 30% of the adult population in the UK are living with obesity and this is expected to rise to 55% by 2050. Obesity-related excess oestrogen, hyperinsulinaemia and chronic inflammation promote endometrial proliferation, increased cell turnover and malignant transformation and is estimated to account for 40–50% of all endometrial cancer cases [[5](https://www.nature.com/articles/s41416-026-03579-8#ref-CR5 "Crosbie EJ, Zwahlen M, Kitchener HC, Egger M, Renehan AG. Body mass index, hormone replacement therapy and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev. 2010;19:3119–30."), [6](https://www.nature.com/articles/s41416-026-03579-8#ref-CR6 "Renehan AG, Soerjomataram I, Tyson M, Egger M, Zwahlen M, Coebergh JW, et al. Incident cancer burden attributable to excess body mass index in 30 European countries. Int J Cancer. 2010;126:692–702.")]. Additional established risk factors include polycystic ovary syndrome, diabetes mellitus, nulliparity, hypertension and tamoxifen exposure [[7](https://www.nature.com/articles/s41416-026-03579-8#ref-CR7 "Raglan O, Kalliala I, Markozannes G, Cividini S, Gunter MJ, Nautiyal J, et al. Risk factors for endometrial cancer: an umbrella review of the literature. Int J Cancer. 2019;145:1719–30.")]. Among genetic predispositions, pathogenic variants affecting the DNA mismatch repair genes (Lynch syndrome) represent the most significant risk factor for endometrial cancer. Approximately 40% of endometrial cancers are classified as copy-number low with no specific molecular profile. These tumours are typically low-grade endometrioid carcinomas and are frequently associated with obesity [[8](https://www.nature.com/articles/s41416-026-03579-8#ref-CR8 "Alexa M, Hasenburg A, Battista MJ. The TCGA molecular classification of endometrial cancer and its possible impact on adjuvant treatment decisions. Cancers \(Basel\). 2021;13:1478.")]. Other molecular phenotypes identified by The Cancer Genome Atlas Research Network include _Polymerase epsilon (POLE)_ -mutant, microsatellite instability (_MMR_ deficient) and copy number high p53 abnormal. Together, this molecular framework enables refined risk stratification and directs adjuvant treatment decisions [[8](https://www.nature.com/articles/s41416-026-03579-8#ref-CR8 "Alexa M, Hasenburg A, Battista MJ. The TCGA molecular classification of endometrial cancer and its possible impact on adjuvant treatment decisions. Cancers \(Basel\). 2021;13:1478."), [9](https://www.nature.com/articles/s41416-026-03579-8#ref-CR9 "Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J, et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Int J Gynecol Cancer. 2016;26:2–30.")]. Endometrial cancer most commonly presents with abnormal uterine bleeding (AUB) including intermenstrual or heavy menstrual bleeding in premenopausal and perimenopausal women and postmenopausal bleeding (PMB) [[10](https://www.nature.com/articles/s41416-026-03579-8#ref-CR10 "Gredmark T, Kvint S, Havel G, Mattsson LA. Histopathological findings in women with postmenopausal bleeding. Br J Obstet Gynaecol. 1995;102:133–6."), [11](https://www.nature.com/articles/s41416-026-03579-8#ref-CR11 "Pennant ME, Mehta R, Moody P, Hackett G, Prentice A, Sharp SJ, et al. Premenopausal abnormal uterine bleeding and risk of endometrial cancer. BJOG. 2017;124:404–11.")]. Approximately 90% of endometrial cancer cases present with PMB; however, only 5-10% of women with PMB are diagnosed with endometrial cancer [[12](https://www.nature.com/articles/s41416-026-03579-8#ref-CR12 "Clarke MA, Long BJ, Del Mar Morillo A, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Association of endometrial cancer risk with postmenopausal bleeding in women: a systematic review and meta-analysis. JAMA Intern Med. 2018;178:1210–22.")]. The further from menopause that an episode of PMB occurs, the more likely the diagnosis of endometrial cancer [[13](https://www.nature.com/articles/s41416-026-03579-8#ref-CR13 "Van Doorn HCOB, Jitze Duk M, Kruitwagen RFMP, Dijkhuizen FPHLJ, Mol BW. The relation between age, time since menopause and endometrial cancer in women with postmenopausal bleeding. Int J Gynecol Cancer. 2007;17:1118–23.")]. Less commonly, patients may present with non-specific symptoms such as abdominal distention or pain, bladder or bowel dysfunction or haematuria [[14](https://www.nature.com/articles/s41416-026-03579-8#ref-CR14 "Kodama J, Seki N, Ojima Y, Nakamura K, Hongo A, Hiramatsu Y. Correlation of presenting symptoms and patient characteristics with endometrial cancer prognosis in Japanese women. Int J Gynaecol Obstet. 2005;91:151–6."), [15](https://www.nature.com/articles/s41416-026-03579-8#ref-CR15 "Pakish JB, Lu KH, Sun CC, Burzawa JK, Greisinger A, Smith FA, et al. Endometrial cancer associated symptoms: a case-control study. J Women’s Health \(Larchmt\). 2016;25:1187–92.")]. Surgery with total hysterectomy and bilateral salpingo-oophorectomy remains the mainstay of curative treatment for endometrial cancer, preferably via minimally invasive approaches with lymph node assessment to guide staging and prognosis. Adjuvant therapy, selected according to stage, grade, histology and molecular profile, reduces recurrence in high-risk disease [[2](https://www.nature.com/articles/s41416-026-03579-8#ref-CR2 "Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399:1412–28."), [16](https://www.nature.com/articles/s41416-026-03579-8#ref-CR16 "Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Radiother Oncol. 2021;154:327–53."), [17](https://www.nature.com/articles/s41416-026-03579-8#ref-CR17 "Njoku K, Barr CE, Crosbie EJ. Current and emerging prognostic biomarkers in endometrial cancer. Front Oncol. 2022;12:890908.")]. Conservative management with progestin therapy may be offered to women seeking fertility preservation or to those who are medically unfit for surgery [[2](https://www.nature.com/articles/s41416-026-03579-8#ref-CR2 "Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399:1412–28."), [16](https://www.nature.com/articles/s41416-026-03579-8#ref-CR16 "Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Radiother Oncol. 2021;154:327–53.")]. Disease stage and molecular phenotype are key prognostic markers in endometrial cancer, with advanced-stage and biologically aggressive tumours associated with poorer outcomes. Early detection, particularly of high-risk subtypes, has significant potential to improve survival and to mitigate the impact of the growing burden of the disease on healthcare systems [[2](https://www.nature.com/articles/s41416-026-03579-8#ref-CR2 "Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399:1412–28."), [16](https://www.nature.com/articles/s41416-026-03579-8#ref-CR16 "Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Radiother Oncol. 2021;154:327–53."), [17](https://www.nature.com/articles/s41416-026-03579-8#ref-CR17 "Njoku K, Barr CE, Crosbie EJ. Current and emerging prognostic biomarkers in endometrial cancer. Front Oncol. 2022;12:890908.")]. ## Endometrial cancer diagnostic pathway In the UK, transvaginal ultrasound (TVUS) is the first-line imaging modality for women presenting with AUB [[18](https://www.nature.com/articles/s41416-026-03579-8#ref-CR18 "National Institute for Health and Care Excellence. How should I investigate for the cause of menorrhagia \[Internet\]. London, UK: NICE; 2023 \[Available from: https://cks.nice.org.uk/topics/menorrhagia-heavy-menstrual-bleeding/diagnosis/investigating-the-cause-of-menorrhagia/ ."), [19](https://www.nature.com/articles/s41416-026-03579-8#ref-CR19 "National Institute for Health and Care Excellence. Gynaecological cancers - recognition and referral London, UK: NICE; \[Available from: https://cks.nice.org.uk/topics/gynaecological-cancers-recognition-referral/ . 2021.")]. TVUS is minimally invasive, avoids ionising radiation and allows accurate assessment of endometrial thickness (ET) [[18](https://www.nature.com/articles/s41416-026-03579-8#ref-CR18 "National Institute for Health and Care Excellence. How should I investigate for the cause of menorrhagia \[Internet\]. London, UK: NICE; 2023 \[Available from: https://cks.nice.org.uk/topics/menorrhagia-heavy-menstru
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