Molecular phenotype of high-grade endometrioid carcinoma of the endometrium

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.

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.

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.

The expression of a complex of multifunctional markers was evaluated in ECE cells of different malignancy stage: p53, FOXP3, p21^WAF1/CIP1, р16^INK4a, 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.

The molecular phenotype of ECE, most informative in terms of specificity and sensitivity (95%) - р5^highFOXP3^lowc-Myc^high, was first characterized, which would help identify a high-grade subtype of this cancer form.