Molecular phenotype of high-grade endometrioid carcinoma of the endometrium
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-4.15450Keywords:
endometrioid carcinoma of the endometrium, expression of biomarkers, informative relevance, molecular phenotypeAbstract
Summary. Background: Prognosis of the course of tumor progression is one of urgent problems of clinical oncology. A relevant specificity of endometrial cancer is its clinical polymorphism within the same histological type of the disease. The search for molecular-biological features associated with the aggressive phenotype of endometrioid carcinomas is indisputably urgent. Aim: To study molecular-biological features of endometrioid carcinoma of the endometrium (ECE) and to identify the molecular subtype of tumors with high potential of malignancy. Materials and Methods: Surgical specimens of 127 patients with EC, stages I–II, aged 36–72 (the average age — 59.3 ± 3.2) were studied using morphological and immunohistochemical methods. The multivariant analysis with the Kullback’s informative measure and PanelomiX were used to estimate the significance of the expression of specific biomarkers. Results: The expression of a complex of multifunctional markers was evaluated in ECE cells of different malignancy stage: p53, FOXP3, p21WAF1/CIP1, р16INK4a, E2F1, cyclins Е and D1, Her2/neu, с-Myc, Е-cadherin, β-catenin, vimentin, CD44, CD24. A triad of biomarkers with threshold expression levels was determined (р53 > 45%; FOXP3 < 14%; с-Myc > 10%). The high expression of oncogene c-Myc and oncosuppressor p53 along with the low level of FOXP3 in tumor cells of ECE was associated with high proliferative potential, low differentiation grade, and deep invasion of a tumor into the myometrium. Conclusions: The molecular phenotype of ECE, most informative in terms of specificity and sensitivity (95%) — р53highFOXP3lowc-Mychigh, was first characterized, which would help identify a high-grade subtype of this cancer form.
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