PROGNOSTIC MOLECULAR-BIOLOGICAL MARKERS OF MALIGNANT FIBROUS HISTIOCYTOMA
DOI:
https://doi.org/10.32471/oncology.2663-7928.t-21-3-2019-g.7267Keywords:
cell cycle phases, malignant fibrous histiocytoma, miRNA, molecular markers, prognosis, proliferative activity, Кі-67Abstract
Malignant fibrous histiocytoma (MFH) is one of the most common tumors of soft tissues in adults. The variation in the course of MFH requires the search for additional markers associated with the development of relapses of this nosological entity of oncopathology. Aim: to investigate the molecular-biological and epigenetic features of primary and recurrent MFH. Materials and methods: a retrospective study was conducted on the clinical material of 46 patients with MFH (TIIbN0M0; stage II) with a verified pathomorphological diagnosis of MFH. The content of DNA in tumor cells was determined by flow cytometry, the content in the tumor cells of the proliferation marker KI-67 was determined by immunohistochemical method, the content in the cells of miR-182, miR-199a and miR-34a was determined by reverse transcription polymerase chain reaction. Results: characteristic of molecular-biological signs and epigenetic features of primary and recurrent MFH were studied. It has been found that recurrent MFH is a heterogeneous neoplasm group that contains both diploid and aneuploid tumor types and is characterized by high proliferative activity. The association of the expressions of miR-34a, -182 and 34a, -182 and -199a with the degree of differentiation and proliferative activity of MFH has been proved. Conclusions: the findings are important for understanding the malignant phenotype of MFH and can also be used to develop a marker panel to predict the aggressiveness of the MFH flow. Based on the obtained data, an algorithm for predicting the aggressiveness of the flow of MFH has been developed.
References
Makis W, Samji K, Hung RW, Deschenes J. Pleomorphic spindle cell sarcoma (PSCS) (formerly known as malignant fibrous histiocytoma, MFH) of the spleen, mimics an atypical haemangioma on 99mTc-RBC, CT and Ultrasound: staging with 18F-FDG PET/CT. BJR Case Rep 2017; 3 (3): 20150519.
Wang Y, Huang L, Lv H, et al. Primary malignant fibrous histiocytoma of the thyroid: two case reports and review of the literature. J Ultrasound Med 2017; 36 (3): 665–9.
Wuyang J, Miner Z, Yan Y, et al. Primary malignant fibrous histiocytoma of the colon: A case report and review of the literature. Mol Clin Oncol 2016; 4: 1006–8.
Coşgun T, Tezel Y, Akyıl M, et al. Primary pulmonary malignant fibrous histiocytoma. Turk Thorac J 2017; 18: 54–6.
Xiongfei L, Renwang L, Tao S, et al. Primary pulmonary malignant fibrous histiocytoma: case report and literature review. J Thorac Dis 2017; 9 (8): 702–8.
Livak KJ, Kenneth J, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 2008; 25 (4): 402–8.31. Chitturi RT, Nirmal RM, Sunil PM, et al. Evaluation of ploidy status using DNA-image cytometry of exfoliated mucosal cells in oral lichen planus. J Cytol 2014; 31 (3): 131–5.
Kim Y, He YY. Ultraviolet radiation-induced non-melanoma skin cancer: Regulation of DNA damage repair and inflammation. Genes Dis 2014; 1 (2): 188–98.
Owens MA, Loken MR. Flow cytometry principles for clinical laboratory practice. Quality Assurance for Quantitative Immunophenotyping. Wiley-Liss: Inc, 1995. 120 p.35. Michels J, Duigou F, Marnay J, et al. Flow cytometry in primary breast carcinomas: prognostic impact of multiploidy and hypoploidy. Cytometry Part B. Clinical Cytometry 2003; 55B: 37–45.
Menon SS, Guruvayoorappan C, Sakthivel KM, Rasmi RR. Ki-67 protein as a tumour proliferation marker. Clin Chim Acta 2019; 491: 39–45.
Sobecki M, Mrouj K, Colinge J, et al. Cell-cycle regulation accounts for variability in Ki-67 expression levels. Cancer Res 2017; 77 (10): 2722–34.
Guled M, Pazzaglia L, Borze I, et al. Differentiating soft tissue leiomyosarcoma and undifferentiated pleomorphic sarcoma: A miRNA analysis. Genes, Chromosomes Cancer 2014; 53: 693–702.
Sachdeva M, Cardona DM, Kirsch DG. MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes. J Clin Invest 2014; 124 (10): 4305–19.
Dhungel B, Ramlogan-Steel CA, Layton CJ, Steel JC. MicroRNA199a-based post-transcriptional detargeting of gene vectors for hepatocellular carcinoma. Mol Ther Nucleic Acids 2018; 13: 78–88.
Wang Y, Cheng Q, Liu J, Dong M. Leukemia stem cell-released microvesicles promote the survival and migration of myeloid leukemia cells and these effects can be inhibited by microRNA34a overexpression. Stem Cells Int 2016; 2016. Article ID 9313425.
Xie W, Wang L, Sheng H, et al. Metformin induces growth inhibition and cell cycle arrest by upregulating microRNA34a in renal cancer cells. Med Sci Monit 2017; 23: 29–37.
