Epithelial Mesenchymal Transition Markers as Relevant Parameters for Risk Stratification of Poor Clinical Outcomes in Patients with Early-Stage Cutaneous Melanoma
https://doi.org/10.35401/2541-9897-2025-10-3-45-51
Abstract
Objective: To evaluate the prognostic significance of Epithelial Mesenchymal Transition (EMT) transition markers and their association with clinicopathological characteristics of cutaneous melanoma.
Materials and Methods: Histopathological and immunohistochemical examination of primary tumor tissue samples was performed in 101 patients with cutaneous melanoma of stage pT1a–1b. The study evaluated the expression of E-cadherin, TWIST, vimentin, Ki-67, Melan-A, and S100 markers.
Results: A significant correlation was identified between the expression of TWIST, vimentin, and E-cadherin and the depth of tumor invasion, primary tumor ulceration, and risk of progression. Disease progression was observed in patients with TWIST and vimentin expression levels > 20%, and E-cadherin expression < 80%. Ulceration of the skin was significantly associated with enhanced EMT features and a greater risk of metastatic dissemination.
Conclusion: The analysis of the obtained results confirms the clinical significance of epithelial–mesenchymal transition markers as independent predictors of disease outcome, also emphasizes the key role of ulceration as an important morphological risk factor for disease progression. The proposed prognostic model, based on the assessment of relative expression levels of TWIST, vimentin, and E-cadherin, provides reliable classification of patients according to their risk of complication development.
About the Authors
E. A. Pasechnikova
Kuban State Medical University; Clinical Oncology Dispensary No. 1
Russian Federation
Russian Federation
Elizaveta A. Pasechnikova, Oncologist, ; Assistant of the Department of Oncology with a Course of Thoracic Surgery
ulitsa Mitrofana Sedina 4, Krasnodar, 35
D. V. Kadomtsev
Clinical Oncology Dispensary No. 1
Russian Federation
Russian Federation
Dmitry V. Kadomtsev, Oncologist
ulitsa Mitrofana Sedina 4, Krasnodar, 35
V. A. Porhanov
Kuban State Medical University; Scientific Research Institute – Ochapovsky Regional Hospital No. 1
Russian Federation
Russian Federation
Vladimir A. Porhanov, Dr. Sci. (Med.), Professor, Academician of Russian Academy of Science, Chief Physician; Head of the Department of Oncology with a Course of Thoracic Surgery
Krasnodar
S. D. Maksimenko
Clinical Oncology Dispensary No. 1
Russian Federation
Russian Federation
Sofia D. Maksimenko, Pathologis
ulitsa Mitrofana Sedina 4, Krasnodar, 350063
References
1. Georgieva A, Pasechnikova E, Kadomtsev D, Maksimenko S, Porkhanov V, Bodnya V, et. al. The Role of the Tumor Microenvironment in the Mechanisms of Carcinogenesis. Modern Problems of Science and Education. 2025;1:74. https://doi.org/10.17513/spno.33892
2. Pasechnikova E.A., Bodnya V.N., Sharov S.V., Kadomtsev D.V., Georgieva A.Y., Stukan A.I. Liquid biopsy: the current state of the issue. Innovative Medicine of Kuban. 2021;(3):57-63. (In Russ.) https://doi.org/10.35401/2500-0268-2021-23-3-57-63
3. Pasechnikova E.A., Bodnya V.N., Kadomtsev D.V., Georgieva A.Yu., Porhanov V.A., Shevchuk D.D. The epithelial-tomesenchymal transition in cancer: pathogenetic features. Innovative Medicine of Kuban. 2022;(2):85-92. (In Russ.) https://doi.org/10.35401/2541-9897-2022-25-2-85-92
4. Eggermont AM. Adjuvant therapy of malignant melanoma and the role of sentinel node mapping. Recent Results Cancer Res. 2000;157:178-189. PMID: 10857171. https://doi.org/10.1007/978-3-642-57151-0_15
5. Hintsala HR, Haapasaari KM, Soini Y, Karihtala P. An immunohistochemical study of NFE2L2, KEAP1 and 8-hydroxy-2’-deoxyguanosine and the EMT markers SNAI2, ZEB1 and TWIST1 in metastatic melanoma. Histol Histopathol. 2017;32(2):129-136. PMID: 27170270. https://doi.org/10.14670/hh-11-778
6. Damsky WE, Rosenbaum LE, Bosenberg M. Decoding melanoma metastasis. Cancers (Basel). 2010;3(1):126-163. PMID: 24212610. PMCID: PMC3756353. https://doi.org/10.3390/cancers3010126
7. Roccuzzo G, Bongiovanni E, Tonella L, et al. Emerging prognostic biomarkers in advanced cutaneous melanoma: a literature update. Expert Rev Mol Diagn. 2024;24(1-2):49-66. PMID: 38334382. https://doi.org/10.1080/14737159.2024.2314574
8. Weiss MB, Abel EV, Mayberry MM, Basile KJ, Berger AC, Aplin AE. TWIST1 is an ERK1/2 effector that promotes invasion and regulates MMP-1 expression in human melanoma cells. Cancer Res. 2012;72(24):6382-6392. PMID: 23222305. PMCID: PMC3531871. https://doi.org/10.1158/0008-5472.can-12-1033
9. Bertolesi GE, Debnath N, Heshami N, et al. Interplay of Light, Melatonin, and Circadian Genes in Skin Pigmentation Regulation. Pigment Cell Melanoma Res. 2025;38(1):e13220. PMID: 39825699. PMCID: PMC11742648. https://doi.org/10.1111/pcmr.13220
10. Cazzato G, Sgarro N, Casatta N, Lupo C, Ingravallo G, Ribatti D. Epigenetics and Control of Tumor Angiogenesis in Melanoma: An Update with Therapeutic Implications. Cancers (Basel). 2024;16(16):2843. PMID: 39199614. PMCID: PMC11352434. https://doi.org/10.3390/cancers16162843
11. Wawrowicz K, Durak-Kozica M, Wierzbicki M, Stępień EŁ. Developing a Tumor Microenvironment in Rotating Human Melanoma Cell Cultures: Study of a Novel Preclinical Model. ACS Omega. 2025;10(25):27288-27300. PMID: 40621031. PMCID: PMC12223851. https://doi.org/10.1021/acsomega.5c02682
12. Pillai M, Rajaram G, Thakur P, et al. Mapping phenotypic heterogeneity in melanoma onto the epithelial-hybrid-mesenchymal axis. Front Oncol. 2022;12:913803. PMID: 36003764. PMCID: PMC9395132. https://doi.org/10.3389/fonc.2022.913803
13. Falcone I, Conciatori F, Bazzichetto C, et al. Tumor Microenvironment: Implications in Melanoma Resistance to Targeted Therapy and Immunotherapy. Cancers (Basel). 2020;12(10):2870. PMID: 33036192. PMCID: PMC7601592. https://doi.org/10.3390/cancers12102870
14. De Oliveira Filho RS, de Oliveira DA, Nisimoto MM, Marti LC. A Review of Advanced Cutaneous Melanoma Therapies and Their Mechanisms, from Immunotherapies to Lysine Histone Methyl Transferase Inhibitors. Cancers (Basel). 2023;15(24):5751. PMID: 38136297. PMCID: PMC10741407. https://doi.org/10.3390/cancers15245751
15. Centeno PP, Pavet V, Marais R. The journey from melanocytes to melanoma. Nat Rev Cancer. 2023;23(6):372-390. PMID: 37095242. https://doi.org/10.1038/s41568-023-00565-7
16. Li Y, Wang Z, Ajani JA, Song S. Drug resistance and Cancer stem cells. Cell Commun Signal. 2021;19(1):19. PMID: 33588867. PMCID: PMC7885480. https://doi.org/10.1186/s12964-020-00627-5
17. Pinzani P, D’Argenio V, Del Re M, et al. Updates on liquid biopsy: current trends and future perspectives for clinical application in solid tumors. Clin Chem Lab Med. 2021;59(7):1181-1200. PMID: 33544478. https://doi.org/10.1515/cclm-2020-1685
18. Pearlman RL, Montes de Oca MK, Pal HC, Afaq F. Potential therapeutic targets of epithelial-mesenchymal transition in melanoma. Cancer Lett. 2017;391:125-140. PMID: 28131904. PMCID: PMC5371401. https://doi.org/10.1016/j.canlet.2017.01.029
Review
For citations:
Pasechnikova E.A., Kadomtsev D.V., Porhanov V.A., Maksimenko S.D. Epithelial Mesenchymal Transition Markers as Relevant Parameters for Risk Stratification of Poor Clinical Outcomes in Patients with Early-Stage Cutaneous Melanoma. Innovative Medicine of Kuban. 2025;10(3):45-51. (In Russ.) https://doi.org/10.35401/2541-9897-2025-10-3-45-51
Views:
20
Email this article 
