Breast cancer (BC) is one of the most frequently diagnosed oncological diseases and the leading cause of cancer death among women worldwide. It is defined as a group of diseases with variable morphology, molecular features, behavior, and response to therapy. With the increasing possibilities of treatment in the era of precision medicine, traditional clinicopathological prognostic variables and established molecular prognostic markers seem insufficient to reflect such a degree of heterogeneity. Additional molecular markers are needed for a personalized approach to therapy, and prognostic biomarkers are necessary to improve cancer treatment. Therefore, molecular morphopathology takes a prominent place in tumor prognosis. Differences in the expression of markers such as epithelial cadherin (E- cadherin), which plays an important role in the process of cell adhesion, is a powerful suppressor of invasion and metastasis, cyclooxygenase-2 (COX-2) and its important role in tumor transformation, cell proliferation and neovascularization, distribution of infiltrating tumor lymphocytes, density and intensity of their expression, may explain why tumors that are comparable in prevalence and histological structure differ in the course of the disease.
Thus, establishing of clinical-morphological, ultrastructural and immunohistochemical features of molecular subtypes of invasive ductal carcinoma and the study of their connection with known prognostic factors will help to determine the course of the disease and will become the basis for personalized treatment to prevent the development of recurrence and metastases in patients with invasive ductal carcinoma. The goal was achieved by using a complex of modern research methods of invasive ductal breast carcinoma: histological, immunohistochemical, electron microscopic, morphometric, and statistical processing of digital data. Scientific novelty of the obtained results. For the first time, it has been shown that infiltrative ductal carcinoma of the breast demonstrates heterogeneity in the morphological structure and ultrastructure of the invasive component depending on the molecular subtype. It has been shown that luminal breast cancers are diverse in terms of the morphological structure of the invasive component, and a significant predominance of one type of the morphological structures has been determined in triple-negative breast cancer by 1.9 times compared to Her-2/neu+ subtype, by 5 times compared to luminal A subtype, and by 4.4 times compared to luminal B subtype (p<0.05). Scientific data on the ultrastructure of the cell surface of infiltrative ductal breast cancer have been supplemented. It has been established that a decrease or absence of asymmetric microvilli on the cell surface was diagnosed at degrees of malignancy G2 and G3. Expression levels of E-cadherin, COX-2, CD31, lymphoid inflammatory infiltration in molecular subtypes of infiltrative ductal breast cancer and their relationship with known prognostic factors were determined. Scientific data on the morphological features of microvessels in the invasive component have been refined, confirming the presence of multiple atypical dilated capillaries and structures with partial endothelial lining in the intratumoral stroma in triple-negative and Her2/neu+ molecular subtypes.
For the first time, the features of the lymphoid microenvironment were established and the distribution of tumor-infiltrating T- and B-lymphocytes and NK- cells in different molecular subtypes was evaluated, as evidenced by the significant predominance of the density of T- and B-lymphocytes intratumorally and near the invasive edge in non-luminal subtypes compared to luminal A and B; the density of intratumoral T-lymphocytes was the highest in triple-negative cancer and was significantly greater than the density in luminal subtype A (p < 0.01). Correlative and combined relationships between the expression of markers characterizing the invasive properties of the tumor and known prognostic factors of the course of the disease were studied. For the first time, the influence of independent clinical and pathogistological factors on the level of lymphocytes (intratumoral and at the invasive edge) in luminal and non-luminal carcinomas of the breast was established on the model for predicting the levels of tumor-infiltrating lymphocytes.
