Prognosis role of epitelial-mezenchimal transformation markers and surface stem tumor cells in the reccurence of serous low grade ovarian carcinomas
Ovarian cancer remains one of the most fatal pathologies among women around the world due to late diagnosis on the advanced stages of the tumor process. Serous ovarian carcinomas (SOC) often recur, which worsens the prognosis for patients’ recovery and survival. The identification of prognostic clinical and morphological factors that predict the appearance of recurrence remains an urgent problem.
The aim of the research was studying relationships between the phenomenon of epithelial-mesenchymal transformation (EMT) and the expression of surface cancer stem cells (CSCS) markers to identify recurrence predictors among women with low grade serous ovarian carcinomas (LGSC).
The material were paraffin blocks and slides of 43 patients with LGSC I-IV FIGO stage. The study included 30 cancers without recurrence and 13 tumors with it within 24 months. The expression of E-cadherin, Vimentin, CD44 and CD117 was studied using immunohistochemical (IHC) method.
Results. Development of recurrence is typical for women with stage III-IV (p=0,01), the expression of Vimentin at level 51–100 % (p=0,001) and E-cadherin at 10–50 % (p=0.04). CD44 was expressed in 51.16 % of tumors and level didn`t depend on age, recurrence, but depended on disease stage (p=0.001). Recurrent LGSCs are characterized by the expression of CD117> 10 % (p=0.0001), its direct correlation with the stage (p=0.0001) and the recurrence (p=0.0001). A direct relationship was found between the CD117 and Vimentin expression.
Conclusions. Prognostic markers of recurrence should be considered stage III-IV, levels of Vimentin 51–100 %, E-cadherin 10-50 % and CD117> 10 %. A correlation between CD117 and Vimentin expression indicates the commonality of EMT and CSCS in progression and recur. CD44 has no independent prognostic role.
Klemba, A., Purzycka-Olewiecka, J. K., Wcisło, G., Czarnecka, A. M., Lewicki, S., Lesyng, B. et. al. (2018). Surface markers of cancer stem-like cells of ovarian cancer and their clinical relevance. Współczesna Onkologia, 2018 (1), 48–55. doi: http://doi.org/10.5114/wo.2018.73885
Ahmed, N., Kadife, E., Raza, A., Short, M., Jubinsky, P. T., Kannourakis, G. (2020). Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods. Cells, 9 (3), 719. doi: http://doi.org/10.3390/cells9030719
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68 (6), 394–424. doi: http://doi.org/10.3322/caac.21492
Cancer in Ukraine, 2019–2020. (2021). National Cancer Institute. Kyiv. Available at: http://www.ncru.inf.ua/publications/BULL_22/index.htm
Cannistra, S. A., Abu-Jawdeh, G., Niloff, J., Strobel, T., Swanson, L., Andersen, J., Ottensmeier, C. (1995). CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors. Journal of Clinical Oncology, 13 (8), 1912–1921. doi: http://doi.org/10.1200/jco.1918.104.22.1682
Sillanpää, S., Anttila, M. A., Voutilainen, K., Tammi, R. H., Tammi, M. I., Saarikoski, S. V., Kosma, V. M. (2003). CD44 Expression Indicates Favorable Prognosis in Epithelial Ovarian Cancer. Clinical Cancer Research, 9 (14), 5318–5324.
Goulding, E. A., Simcock, B., McLachlan, J., Griend, R., Sykes, P. (2019). Low‐grade serous ovarian carcinoma: A comprehensive literature review. Australian and New Zealand Journal of Obstetrics and Gynaecology, 60 (1), 27–33. doi: http://doi.org/10.1111/ajo.13105
Eun, K., Ham, S. W., Kim, H. (2017). Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting. BMB Reports, 50 (3), 117–125. doi: http://doi.org/10.5483/bmbrep.2017.50.3.222
Garson, K., Vanderhyden, B. C. (2015). Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm. Reproduction, 149 (2), R59–R70. doi: http://doi.org/10.1530/rep-14-0234
Kaldawy, A., Segev, Y., Lavie, O., Auslender, R., Sopik, V., Narod, S. A. (2016). Low-grade serous ovarian cancer: A review. Gynecologic Oncology, 143 (2), 433–438. doi: http://doi.org/10.1016/j.ygyno.2016.08.320
Katsoulis, M., Lekka, J., Vlachonikolis, I., Delides, G. (1995). The prognostic value of morphometry in advanced epithelial ovarian cancers. British Journal of Cancer, 72 (4), 958–963. doi: http://doi.org/10.1038/bjc.1995.441
Karan Križanac, D., Krasić Arapović, A., Skočibušić, S., Pintarić, I., Trgo, G., Tomić, S. (2018). CD44 Immunoexpression is Unfavorable Predictor in Ovarian Serous Cancer. Applied Immunohistochemistry & Molecular Morphology, 26 (6), 398–402. doi: http://doi.org/10.1097/pai.0000000000000427
Lisio, M.-A., Fu, L., Goyeneche, A., Gao, Z., Telleria, C. (2019). High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints. International Journal of Molecular Sciences, 20 (4), 952. doi: http://doi.org/10.3390/ijms20040952
Muñoz-Galván, S., Carnero, A. (2020). Targeting Cancer Stem Cells to Overcome Therapy Resistance in Ovarian Cancer. Cells, 9 (6), 1402. doi: http://doi.org/10.3390/cells9061402
Pastushenko, I., Blanpain, C. (2019). EMT Transition States during Tumor Progression and Metastasis. Trends in Cell Biology, 29 (3), 212–226. doi: http://doi.org/10.1016/j.tcb.2018.12.001
Rosso, M., Majem, B., Devis, L., Lapyckyj, L., Besso, M. J., Llauradó, M. et. al. (2017). E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness. PLOS ONE, 12 (9), e0184439. doi: http://doi.org/10.1371/journal.pone.0184439
Solopova, A. G., Bitsadze, V. O., Solopova, A. E., Makatsariya, A. D., Rozanov, I. A. (2017). Ovarian cancer: current approaches to classification, diagnostics, staging and differential management of patients. Journal of Obstetrics and Women’s Diseases, 66 (2), 55–66. doi: http://doi.org/10.17816/jowd66255-66
Suster, N. K., Virant-Klun, I. (2019). Presence and role of stem cells in ovarian cancer. World Journal of Stem Cells, 11 (7), 383–397. doi: http://doi.org/10.4252/wjsc.v11.i7.383
Herrington, C. S. (Ed.) (2020). WHO Classification of Tumours Female Genital Tumours. Lyon: International Agency for Research on Cancer, 44–46.
Ryabtseva, O. D., Antipova, S. V., Lukyanova, N. Yu., Nadirashvili, M. A., Polishchuk, L. Z., Chekhun, V. F. (2014). Individual prognosis of serous ovarian cancer survival patients based on adhesion and proliferation of tumor cells. Oncology, 16 (1). Available at: https://www.oncology.kiev.ua/ru/article/6303/individualnij-prognoz-vizhivanosti-xvorix-z-uraxuvannyam-proliferacii-ta-adgezii-puxlinnix-klitin-u-xvorix-na-seroznij-rak-yayechnika-2
Copyright (c) 2021 Varvara Hryhorenko
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.
Authors, who are published in this journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons CC BY, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.