The influence of selected immunohistochemical and clinical-pathological markers on the prognosis of patients with malignant uterine tumors

Česká verze

Authors: Petra Herboltová ^1,2 ; Petra Ovesná ³ ; Klára Dvořáková ⁴; Tibor Focko ²; Radovan Kaštan ⁴; Petr Stráník ¹ ; Vendula Smoligová ¹ ; Jan Kosťun ¹ ; Jiří Presl ¹
Authors place of work: Gynekologicko-porodnická klinika LF UK a FN Plzeň ¹; Gynekologicko-porodnické oddělení, Nemocnice Jihlava, p. o. ²; Institut bio statistiky a analýz, LF MU, Brno ³; Patologicko-anatomické oddělení, Nemocnice Jihlava, p. o. ⁴
Published in the journal: Ceska Gynekol 2025; 90(6): 425-434
Category: Původní práce
doi: https://doi.org/10.48095/cccg2025425

Summary

Introduction: Endometrial carcinoma is the most common gynecological malignancy in developed countries, and its incidence has been increasing in recent decades. The prognosis of patients depends on a combination of clinical-pathological characteristics, and more recently, molecular indicators. The aim of this study was to analyze the influence of the selected prognostic markers –⁠ immunohistochemical (L1CAM, ER, PR) and classical (FIGO stage, grade, myometrial invasion, lymph node involvement, distant metastases) –⁠ on the survival of patients with endometrial carcinoma. Materials and methods: A retrospective evaluation was performed on 143 women with histologically confirmed endometrial cancer treated between 2014 and 2018. All patients underwent primary surgical treatment. Resected specimens were subjected to immunohistochemical analysis of L1CAM, ER, and PR. Data were statistically processed using a Kaplan-Meier analysis and the Cox proportional hazards model, adjusted to age. Results: L1CAM expression was detected in 14% of patients and was associated with shortened survival (HR ≈ 3.9). ER and PR positivity (89% and 85%, resp.) correlated with a more favorable prognosis (HR for ER positivity 0.21; PR 0.23). Classical factors such as higher grade, advanced FIGO stage, cervical and lymphovascular invasion, or presence in nodes were statistically associated with worse survival. An interesting finding was a significantly better prognosis in asymptomatic patients –⁠ the presence of symptoms increased the risk of death up to fourfold. Conclusion: L1CAM positivity and loss of hormone receptors are significant adverse prognostic factors. Their inclusion in routine immunohistochemical panel testing improves risk stratification and treatment personalization, which at the time of publication of this paper is already included in the updated ESGO-ESTRO-ESP 2025 guidelines. At the same time, it has been shown that the absence of symptoms at diagnosis is a favorable survival indicator. The results support further research into prognostic markers and their integration into clinical decision-making algorithms.

Keywords:

symptoms – Endometrial carcinoma – survival – L1 cell adhesion molecule – estrogen receptors – progesterone receptors

Zdroje

1. Amant F, Mirza MR, Koskas M et al. Cancer of the corpus uteri. Int J Gynecol Obstet 2018; 43 (Suppl 2): 37–50. doi: 10.1002/ijgo. 12612.

2. Berek JS, Matias-Guiu X, Creutzberg C et al. FIGO staging of endometrial cancer: 2023. J Gynecol Oncol 2023; 34 (5): e85. doi: 10.3802/jgo. 2023.34.e85.

3. Makker V, MacKay H, Ray-Coquard I et al. Endometrial cancer. Nat Rev Dis Primers 2021; 7 (1): 88. doi: 10.1038/s41572-021-00324-8.

4. Concin N, Matias-Guiu X, Cibula D et al. ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025. Lancet Oncol 2025; 26 (8): e423–e435. doi: 10.1016/S1470-2045 (25) 00167-6.

5. Colombo N, Creutzberg C, Amant F et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Ann Oncol 2016; 27 (1): 16–41. doi: 10.1093/annonc/mdv484. Erratum in: Ann Oncol 2017; 28 (suppl_4): iv167–iv168. doi: 10.1093/annonc/mdx258.

6. International Agency For Research on Cancer: Female Genital Tumours. WHO Classification of Tumours. 5th ed, vol. 4. USA: WHO 2020 : 391–418.

7. SVOD. 2025 [online]. Dostupné z: www.svod.cz.

8. National Comprehensive Cancer Network. NCCN guidelines: uterine neoplasms. 2025 [online]. Available from: www.nccn.org.

9. Zikán M et al. Onkogynekologie. Praha: Maxdorf 2024.

10. Concin N, Matias-Guiu X, Vergote I et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 2021; 31 (1): 12–39. doi: 10.1136/ijgc-2020-002230.

11. Kandoth C, Schultz N, Cherniack A et al. The Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497 (7447): 67–73. doi: 10.1038/nature12113.

12. Van Gool IC, Stelloo E, Nout RA et al. Prognostic significance of L1CAM expression and its association with mutant p53 expression in high -⁠ -risk endometrial cancer. Mod Pathol 2016; 29 (2): 174–181. doi: 10.1038/modpathol.2015.147.

13. Bosse T, Nout R, Stelloo E et al. L1 cell adhesion molecule is a strong predictor for distant recurrence and overall survival in early stage endometrial cancer: pooled PORTEC trial results. Eur J Cancer 2014; 50 (15): 2602–2610. doi: 10.1016/j.ejca.2014.07.014.

14. Weinberger V, Bednarikova M, Hausnerova J et al. A novel approach to preoperative risk stratification in endometrial cancer: the added value of immunohistochemical markers. Front Oncol 2019; 9 : 265. doi: 10.3389/fonc.2019.00265.

15. Frühauf F, Dvořák M, Haaková L et al. Ultrazvukový staging karcinomu endometria –⁠ doporučená metodika vyšetření. Ceska Gynekol 2014; 79 (6): 466–476.

16. Frühauf F, Zikán M, Semerádová I et al. The diagnostic accuracy of ultrasound in assessment of myometrial invasion in endometrial cancer: subjective assessment versus objective techniques. Biomed Res Int 2017; 2017 : 1318203. doi: 10.1155/2017/1318203.

17. Kurman RJ, Carcangiu ML, Herrington CS. WHO Classification of Tumours of Female Reproductive Organs. 4th ed, vol 6. USA: WHO 2014 : 208–227.

18. Koh WJ, Greer BE, Abu-Rustum NR et al. Uterine neoplasms, version 1.2014. J Natl Compr Canc Netw 2014; 12 (2): 248–280. doi: 10.6004/jnccn.2014.0025.

19. Smogeli E, Davidson B, Cvancarova M et al. L1CAM as a prognostic marker in stage I endometrial cancer: a validation study. BMC Cancer 2016; 16 : 596. doi: 10.1186/s12885-016 -⁠ 2631-4.

20. van der Putten LJ, Visser NC, van de Vijver et al. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study. Br J Cancer 2016; 115 (6): 716–724. doi: 10.1038/bjc. 2016.235.

21. Kommoss FK, Karnezis AN, Kommoss F et al. L1CAM further stratifies endometrial carcinoma patients with no specific molecular risk profile. Br J Cancer 2018; 119 (4): 480–486. doi: 10.1038/s41416-018-0187-6.

22. van den Heerik AS, Horeweg N, Nout RA et al. PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer 2020; 30 (12): 2002–2007. doi: 10.1136/ijgc-2020 -⁠ 001929.

23. Vrede SW, Van Weelden WJ, Bulten J et al. Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer. Gynecol Oncol 2025; 192 : 15–23. doi: 10.1016/j.ygyno.2024. 10.028.

24. van der Putten LJ, Visser NC, van de Vijver K et al. Added value of estrogen receptor, progesterone receptor, and L1 cell adhesion molecule expression to histology-based endometrial carcinoma recurrence prediction models: an ENITEC collaboration study. Int J Gynecol Cancer 2018; 28 (3): 514–523. doi: 10.1097/IGC.0000000 000001187.

ORCID autorů

P. Herboltová 0000-0003-3689-1004

P. Ovesná 0000-0002-3547-5896

P. Stráník 0009-0009-7077-2448

V. Smoligová 0009-0006-4614-5418

J. Kosťun 0000-0003-4077-9031

J. Presl 0000-0001-7632-4069

Doručeno/Submitted: 14. 9. 2025

Přijato/Accepted: 16. 9. 2025

MUDr. Petra Herboltová

Gynekologicko-porodnické oddělení

Nemocnice Jihlava, p. o.