Morphological characteristics and expression of adhesion markers in cells of low differentiated endometrial carcinoma

Abstract

Summary. The aim of the study was to evaluate the morphological features of endometrioid carcinoma of the endometrium (ECE) of low differentiation grade with different invasive potential and to characterize their molecular phenotype by the expression of a number of adhesion markers. Materials and Methods: We have studied the samples of operation material of 37 patients with ECE of low differentiation grade with deep invasion (> ½ myometrium), n = 26, and with invasion < ½ myometrium, n = 11, with the use of morphological and immunohistochemical methods, and flow cytometry. Results: In the morphological study of tumors with deep invasion in the myometrium, we have detected pronounced structural heterogeneity, which became the basis for the discretion of two groups of tumors with different characteristics of morphological phenotypes. In the majority of cases, solid layers and glandular-like structures are detected, and the similarity of the tumor epithelium with the elements of the endometrium is completely lost. In such tumors high expression of adhesion molecules – E-cadherin, CD44, CD24, and β-catenin and low expression of the marker of mesenchymal tissues — vimentin were determined. Other tumors were characterized by morphological features of the epithelial-mesenchymal transition (EMT), with the decrease of the expression of E-cadherin, β-catenin, CD24, CD44, and a significant increase in vimentin expression in comparison with these indices in tumors without signs of EMT. In ECEs that invade < ½ myometrium, the morphological indices of malignancy were less pronounced, which was associated by the changes in the expression of the molecular markers. Conclusion: This comprehensive study has established associations between the morphological heterogeneity of ECE and the expression of adhesion markers and vimentin, which is important for understanding the mechanisms of tumor cell migration.

Twist expression and content of tumour-associated macrophages in endometrial carcinoma

“…Such ECEs often had large, convoluted glands, tightly surrounding the myometrium, and "invasive front areas". As it was shown in the authors' previous study while investigating the morphological traits of such neoplasms, they invaded the myometrium by large groups of tumour cells in the form of solid bands which is a morphological manifestation of collective migration [17]. These results agree with the data of other researchers who demonstrated that such morphological traits of ECE are associated with the decreased expression of EMT markers [29,30].…”

“…The data obtained were compared with the results of the previous studies, in which the authors determined the expression of EMT markers in these very cases of ECE [16][17][18].…”

The association of Wnt-signalling and EMT markers with clinical characteristics in women with endometrial cancer

“…Expression of all immunohistochemical markers (β-catenin, Dkk1, E-cadherin and N-cadherin) was evaluated by counting the number of immuno-positive tumor cells and expressed by percentage. Tumor cells were deemed positive if there was a clear membranous (β-catenin) ( 36 , 37 ), membranous and/or cytoplasmic (E-cadherin, N-cadherin) ( 29 , 38 ) and cytoplasmic (Dkk1) ( 10 , 39 , 40 ) reaction. At the same time, intensity of reaction was scored on the scale from 0 to 3 (0 = no reaction, 1 = mild, 2 = moderate, 3 = strong).…”

The Role of CTNNB1 in Endometrial Cancer

“…Florescu et al found significant differences between intensity of membranous β -catenin immunopositivity and degree of tumour differentiation, invasion in the myometrium and tumour stage [ 40 ]. Such findings suggest that decreased expression of β -catenin, characteristic of EMT, could also be determined by IHC methods [ 13 , 40 ]. Machin et al found a correlation between exon 3 mutations of CTNNB1 and nuclear β -catenin immunostaining [ 48 ]; thus, more recent studies tried to validate IHC methods as a surrogate for identification of exon 3 mutations in CTNNB1 [ 44 , 46 , 49 ].…”

“…Most endometrioid tumours have few somatic copy-number alterations (SCNAs) whereas most serous and serous-like tumours exhibit extensive SCNAs, and the extent of SCNA roughly correlates with progression-free survival [ 12 ]. However, there is substantial variability in the clinical course of the disease, associated with both morphological and molecular features of the tumour [ 13 ].…”