Quantitative assesment of coexpression of cytokeratins and mesenchimal cells marker vimentin in serous ovarian cancer

Background. Epithelial-mesenchymal transition (EMT) is a factor related to metastatic potential of tumor cells. The most distinguishing feature of this transformation is expression of protein vimentin, which is not common for epithelial cells. Data of EMT level and clinical significance of the marker is ambiguous in prognosis of tumor different localization including ovarian cancer. Objective is characterization of EMT in ovarian cancer tissue based on quantitative analysis of co-expression level of epithelial cytokeratins and mesenchymal cells marker vimentin. Materials and methods. A quantitative assessment of co-expression level of cytokeratins and vimentin was performed by double immunofluorescence staining method (58 surgery specimens of ovarian cancer stage III), associated with flow cytometry. Results. Double immunofluorescence staining method, developed and used in the current study, was used for quantitative assessment of EMT level based on value of cytokeratin and vimentin co-expression in epithelial cells. Epithelial cells co-expressed these markers, were detected in 100 % tumor investigated with individual value differences from 10 to 86 %. Average co-expression level of cytokeratins and vimentin in subgroups with high and low level value related to median 42 % significantly varied and were 28,5 ± 7,5 and 56,3 ± 11,8 % (p = 0,02) respectively. Conclusions Serous ovarian cancer is molecular heterogeneous group with principal differences in level of EMT tumor phenotype between various patients. In half of the cases the disease is characterized by high metastatic potential of tumor cells. Co-expression of cyto-keratins and vimentin in all the tumors investigated is evidenced clinical significance of this molecular characteristic in ovarian cancer pathogenesis.

рак яичников, эпителиально-мезенхимальный переход, виментин, проточная цитофлуориметрия, ovarian cancer, epithelial-mesenchymal transition, vimentin, flow cytometry

1. Kenda Suster N., Smrkolj S., Virant-Klun I. Putative stem cells and epithelialmesenchymal transition revealed in sections of ovarian tumor in patients with serous ovarian carcinoma using immunohistochemistry for vimentin and pluripotency-related markers. J Ovarian Res 2017; 10(1): 11. DOI: 10.1186/ s13048-017-0306-7. PMID: 28231820.

2. Despierre E., Vergote I., Anderson R. et al. Epidermal Growth Factor Receptor (EGFR) pathway biomarkers in the randomized phase III trial of Erlotinib versus observation in ovarian cancer patients with No evidence of disease progression after first-line platinum-based chemotherapy. Target Oncol 2015; 10(4): 583-96. DOI: 10.1007/s11523-015-0369-6. PMID: 26004768.

3. Li X., Yang J., Wang X. et al. Role of TWIST2, E-cadherin and Vimentin in epithelial ovarian carcinogenesis and prognosis and their interaction in cancer progression. Eur J Gynaecol Oncol 2016; 37(1): 100-8. PMID: 27048119.

4. Davidson B., Holth A., Hellesylt E. et al. The clinical role of epithelialmesenchymal transition and stem cell markers in advanced-stage ovarian serous carcinoma effusions. Hum Pathol 2015; 46(1): 1-8. DOI: 10.1016/j.humpath.2014.10.004. PMID: 25455994.

5. Wu D.I., Liu L., Ren C. et al. Epithelialmesenchymal interconversions and the regulatory function of the ZEB family during the development and progression of ovarian cancer. Oncol Lett 2016; 11(2): 1463-8. PMID: 26893761.

6. Vos M.C., Hollemans E., Ezendam N. et al. MMP-14 and CD44 in Epithelialto-Mesenchymal Transition (EMT) in ovarian cancer. J Ovarian Res 2016; 9(1): 53. DOI: 10.1186/s13048-016-0262-7. PMID: 27590006.

7. Богуш Т.А., Шатурова А.С., Дудко Е.А. и др. Количественная иммунофлуоресцентная оценка с использованием проточной цитофлуориметрии экспрессии эстрогеновых рецепторов ß в солидных опухолях человека. Вестник Московского университета 2011; 52(4): 305-12.