Introduction. The rapid development of basic science enabled us to significantly expand our understanding of various intercellular interactions. Epithelial-mesenchymal transition (EMT) is known to play a key role in certain tissue formation in the embryonic period. However, recent data show that EMT can also be observed in some pathological conditions, in particular, in various neoplasm development. This suggests that there are a number of alternative and fundamentally new mechanisms for the tumor formation and progression. Thus, EMT, which occurs in carcinomas, increases the invasiveness, immunoresistance, immunity to therapy, and the metastatic potential. Knowledge of EMT features and their timely recognition in morphological tumor diagnosis is of great predictive importance for patients. The aim of the research was to study the morphologi-cal features of epithelial-mesenchymal transition in the main types of gastric cancer. Materials and methods. We studied specimens of gastric carcinomas (N=64) including 31 cases of diffuse type, 19 cases of intestinal type, and 14 cases of mixed type. Results. All cases of the diffuse carcinoma group showed spread EMT features, which appeared already in the mucosa and completed with positive vimentin expression in 93.5% of cases. The malignant cell prolifera-tive activity was low; however, in 29% of cases we detected areas of moderate or even high activity. In the intestinal type gastric cancer, EMT developed as a result of tumor progression, it arose more often in the deeper layers and was incomplete and focal. As a rule, the proliferative activity of tumor cells was high and moderate. Vascular invasion occurred more often in diffuse type (90.3%), less often in mixed type (71.4%), and even less often in the intestine type (55.8%) gastric carcinoma. Conclusion. The variety of morphological features of EMT, its frequency, prevalence, completeness, and sequence in the development of various types of gastric cancer determines the features of their clinical manifestation and influences their further management. Keywords: gastric cancer, diagnosis, histological main types, EMT, morphopathology
Relevance. Epithelial-mesenchymal transformation (EMT) largely determines the biological behavior and prognosis of cancers of various localizations. It is known that the determining role in the control and implementation of the transition of the epithelial phenotype to the mesenchymal belongs to the microenvironment. At the same time, the histochemical and microscopic characteristics of stromal elements remain unclear; therefore, the aim of our study was to establish the morphological features of the stroma that affect the development of EMT in lung cancer. Materials and Methods. We studied 32 cases of lung cancer with hematoxylin and eosin staining of sections, Alcian blue at pH 1.0 and 2.5, PAS reaction, as well as immunohistochemical studies with monoclonal antibodies to HMW, AE 1 / AE 3, cytokeratin 18, c-erb B 2, vimentin E-cadherin, alpha-smooth muscle actin, GFAP and chromogranin A, Ki-67. In 16 cases, there was widespread epithelial-mesenchymal transformation (EMT), in 14 cases - focal and in 2 cases EMT was absent. In half of the cases of widespread EMT, it was complete; among the cases of focal EMT, it was not complete. The transition from the epithelial to the mesenchymal phenotype was facilitated by the activation of the stroma, namely, the presence of myofibroblasts and alcianophilia of the extracellular matrix, inflammatory cell infiltration, expression of the epidermal growth factor receptor (c-erb B 2) in stromal cells, proliferation and neurogenic differentiation of stromal cells of stromal cells. Results and Discussion. The activated stroma correlates with the frequency of EMT. Thus, large areas of activated stroma with the presence of myofibroblasts and alcianophilia of the extracellular matrix are more common in cases of widespread EMT (14 out of 16-87.5 %) than in cases of focal EMT (4 out of 14-28.6 %). The differences are statistically significant, p 0.01. Inflammatory cell infiltration, which is the source of a signal for transformation, expression of the epidermal growth factor receptor (c-erb B 2) in stromal cells, proliferation, and neurogenic differentiation of stromal cells also correlated with the frequency of EMT. In all cases, the differences are statistically significant, p0.01. Conclusions. The data obtained indicate the undoubted influence of signals from the activated stroma on the development of epithelial-mesenchymal transformation of tumor cells.
Introduction. Breast cancer is in the first place in the structure of morbidity among all malignant neoplasms in women. The prognosis of the disease depends on the tumor degree, including the presence of epithelial-mesenchymal transformation (EMT), the degree of invasion, the proliferative index, the preservation or absence of estrogen, progesterone, and epidermal growth factor receptors.Aim: To study the immunohistochemical and morphological characteristics of the epithelial-mesenchymal transformation of breast cancer.Material and Methods. Immunohistochemical study with antibodies to AE1/AE3, HMW, CK18, Snail, HER2/neu, E-cadherin, Vimentin, α-SMA, CD34, Ki-67 and p63 was performed in 60 patients of different age with breast cancer. Native preparations were stained with picrofuchsin according to van Gieson Alcian blue. Inflammatory infiltrate cells were examined for antibodies CD45, CD3, CD4, CD8, CD20, CD68.Results. In ductal carcinoma, positive expression for estrogen and progesterone was found in 82.7% and 86.3%, respectively, the proliferation index ranged before 66,6%, and p-53 was positive in 97%. In lobular cancer, positive expression to estrogen and progesterone was observed in 83.4% and 66.6%, respectively, the index of proliferative activity at the level of 50%, and p-53 was positive in 66.6%. Positive moderate expression of HER-2/neu was determined in 47% of ductal and 50% of lobular cancers. Estrogen plays an important role in the development of invasive breast cancer, leads to tumor progression and contributes to EMT. EMT, in turn, leads to the expression of E-cadherin associated with a worse survival prognosis. EMT indirectly leads to the intensification of angiogenesis, and the presence of a large number of newly formed vessels increases the risk of metastasis. Histochemical methods were used to determine the growth of fibrous tissue around invasively growing cancer complexes. Cells located perifocally looked like fibrobla ts, immunohistochemically moderately expressed Vimentin and weakly expressed pancytokeratin, which proved the tumor nature of the cells and the acquisition of mesenchymal features by them. The inflammatory infiltrate along the periphery of the tumor growth consisted mainly of T- and B-lymphocytes, and around the cancer complexes - of B-lymphocytes and macrophages.Conclusion. The study of the immunohistochemical tumor phenotype will make it possible to prescribe adequate polychemotherapy and determine the prognosis of the course of the disease.
Introduction. Breast cancer is in the first place in the structure of morbidity among all malignant neoplasms in women. The prognosis of the disease depends on the tumor degree, including the presence of epithelial-mesenchymal transformation (EMT), the degree of invasion, the proliferative index, the preservation or absence of estrogen, progesterone, and epidermal growth factor receptors.Aim. To study the immunohistochemical and morphological characteristics of the epithelial-mesenchymal transformation of breast cancer.Material and Methods. Immunohistochemical study with antibodies to AE1/AE3, HMW, CK18, Snail, HER2/neu, E-cadherin, Vimentin, α-SMA, CD34, Ki-67 and p63 was performed in 60 patients of different age with breast cancer. Native preparations were stained with picrofuchsin according to van Gieson Alcian blue. Inflammatory infiltrate cells were examined for antibodies CD45, CD3, CD4, CD8, CD20, CD68.Results. In ductal carcinoma, positive expression for estrogen and progesterone was found in 82.7% and 86.3%, respectively, the proliferation index ranged before 66,6 %, and p-53 was positive in 97%. In lobular cancer, positive expression to estrogen and progesterone was observed in 83.4% and 66.6%, respectively, the index of proliferative activity at the level of 50 %, and p-53 was positive in 66.6%. Positive moderate expression of HER-2/neu was determined in 47% of ductal and 50% of lobular cancers. Estrogen plays an important role in the development of invasive breast cancer, leads to tumor progression and contributes to EMT. EMT, in turn, leads to the expression of E-cadherin associated with a worse survival prognosis. EMT indirectly leads to the intensification of angiogenesis, and the presence of a large number of newly formed vessels increases the risk of metastasis. Histochemical methods were used to determine the growth of fibrous tissue around invasively growing cancer complexes. Cells located perifocally looked like fibroblasts, immunohistochemically moderately expressed Vimentin and weakly expressed pancytokeratin, which proved the tumor nature of the cells and the acquisition of mesenchymal features by them. The inflammatory infiltrate along the periphery of the tumor growth consisted mainly of T- and B-lymphocytes, and around the cancer complexes - of B-lymphocytes and macrophages.Conclusion. The study of the immunohistochemical tumor phenotype will make it possible to prescribe adequate polychemotherapy and determine the prognosis of the course of the disease.
Colorectal cancer ranks third in the morbidity structure among all malignant tumors and includes sporadic and hereditary neoplasms. Cancer genome sequencing has revealed numerous mutation variants that determine the ways colorectal carcinoma progresses. The course, prognosis, and management strategy of the disease vary greatly depending on the subtype of a molecular tumor. This literature review discusses the latest data on the variants of colorectal cancer oncogenesis and presents the phenotypic model classification based on them. Immunohistochemistry (IHC) is suggested for determining the individual tumor characteristics. The article also clarifies the Bethesda panel used to detect microsatellite instability, markers for Lynch syndrome, and a list of IHC markers for determining the phenotypic model of colorectal carcinoma. Keywords: colorectal cancer, phenotypic models, consensus molecular subtypes (CMS), immunohisto-chemistry, Bethesda panel, Lynch syndrome
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