The aim of the studywas to summarize data on the role of tumor-associated dendritic cells (DC) in the formation of squamous cell carcinoma microenvironment, their participation in the development of immune inflammatory responses in the tumor stroma and relation to tumor progression.Material and Methods. We analyzed 79 publications available from Pubmed, Google Scholar, Elibrary databases from January 2000 to December 2017.Results. The characteristics of different types of DC, including Langerhans cells (CR), were presented. The different methods of DC identification were described. The information on the presence of DC in squamous cell carcinomas was analyzed. The influence of the tumor on DCs, as well as the relationship between the number and functional characteristics of DCs and invasive/metastatic tumor potentialities was described. The prognostic value of DCs and their effect on disease-free, metastasis-free and overall survival rates were analyzed. The data on the association between DCs and the response to chemoradiotherapy were presented. The analysis of the relationship between the DC characteristics and the development of immuno-inflammatory responses in the tumor microenvironment was carried out.Conclusion. The methodological approaches to the detection of DCs are variable, but the sensitivity of each method, as well as the comparison of different methods for estimating the number and functional characteristics of DCs, have been little studied. There is no data on the relationship between the length of DC dendrites and the parameters of invasive/metastatic tumor potentialities, disease-free, metastasis-free and overall survival rates. Numerous studies indicate the association between the number of DCs and the tumor progression, however these data are contradictory. There is no data about the relationship between the number of DCs and hematogenous metastasis of squamous cell carcinomas. The association of tumor-associated DC with the types of immunoinflammatory responses in the tumor microenvironment has been insufficiently studied.

The relationship between histological and immunohistochemical parameters of synovial sarcoma and Ewing’s sarcoma/PNET and the number of cells carrying the t(X;18)(p11.2;q11.2) translocation. Histological examination was carried out to study the cytotypical characteristics, types of structures of tumor growth, tumor spread and secondary dystrophic changes in the tumor. The tumor mitotic activity was assessed by determining the mitotic index. The presence of markers such as vimentine, desmin, SMA, Myf-4, MyoD1, S-100, CD57, bcl-2, CD99, cytokeratine AE1/AE3, cytokeratine 7, EMA, Synaptophysin, chromogranin and Ki67 was determined by immunohistochemical assay. Detection of translocations characteristic of synovial sarcoma and Ewing’s sarcoma/PNET was performed using chromogenic in situ hybridization. The study results showed the relationship between the histological and immunohistochemical parameters of synovial sarcoma and Ewing’s sarcoma/PNET and the percentage of tumor cells having specific t(X;18)(p11.2;q11.2) translocation.

The study of functional polymorphism of the VEGF-A gene at positions –2578 in the promoter region and +936 in the 3`untranslated region in breast cancer patients with different receptor status of the tumor was undertaken to identify markers associated with risk of breast cancer. DNA samples from 292 women with breast cancer were analyzed. The genotyping of С–2578A and C+936T VEG-FA polymorphisms was performed using the method of restriction analysis of amplification products. The distributions of VEGF-A genotypes in patients having estrogen and progesterone receptors in tumor tissues were investigated and genotypes associated with risk of breast cancer recurrences were detected.

The increased expression levels of Ki67, cyclooxygenase-2 (COX-2) and p16ink4a proteins after neoadjuvant chemotherapy for locally advanced cervical cancer were shown to correlate with unfavorable prognosis. The level of Ki67 expression before treatment was 85 % in patients, who subsequently developed disease progression. The overall 5-year survival rates were significantly higher in cervical cancer patients with Ki67 expression of <50 % than in patients with Ki67 expression >50 %. We found the correlation between COX-2 expression and overall survival of patients with locally advanced cervical cancer. Thus, the 5-year survival rates were 84 % and 66% in cervical cancer patients with COX-2 expressions of <50 % and >50 %, respectively. The correlation between p16ink4a expression and disease-free survival was found.

This review estimates immunohistochemical parameters reflecting apoptotic, proliferative activities, participating in angiogenesis and defining biological behavior of the tumor because treatment outcomes of locally advanced cervical cancer remain poor. Disease recurrences occur within the first two years after treatment in half of the patients. At the same time, many issues concerning the role of various indices of tumor growth as prognostic factors are controversial. Therefore, the study of histological patterns and molecular-biological characteristics of the tumor and their influence on short- and long-term treatment results are of great importance. The study of biological markers for locally advanced cervical cancer will allow physicians to understand tumor status, to predict the disease and to individualize treatment plan.

The relationship between histological and immunohistochemical parameters of synovial sarcoma and Ewing’s sarcoma/PNET and the number of cells carrying the t(X;18)(p11.2;q11.2) translocation. Histological examination was carried out to study the cytotypical characteristics, types of structures of tumor growth, tumor spread and secondary dystrophic changes in the tumor. The tumor mitotic activity was assessed by determining the mitotic index. The presence of markers such as vimentine, desmin, SMA, Myf-4, MyoD1, S-100, CD57, bcl-2, CD99, cytokeratine AE1/AE3, cytokeratine 7, EMA, Synaptophysin, chromogranin and Ki67 was determined by immunohistochemical assay. Detection of translocations characteristic of synovial sarcoma and Ewing’s sarcoma/PNET was performed using chromogenic in situ hybridization. The study results showed the relationship between the histological and immunohistochemical parameters of synovial sarcoma and Ewing’s sarcoma/PNET and the percentage of tumor cells having specific t(X;18)(p11.2;q11.2) translocation.

Впервые проведен анализ связи экспрессии металлопротеиназы PAPP-A с экспрессией инсулиноподобных ростовых (ИФР-I, ИФР-II, VEGF) и транскрипционных (NF-kB, HIF-1) факторов, играющих важную роль в патогенезе рака. Наблюдались положительные связи между уровнем металлопротеиназы PAPP-A и содержанием ростовых (VEGF и ИФР-I) и транскрипционных NF-kB p50, NF-kB p65, HIF-1 факторов. Выявленные корреляции позволяют предположить важную роль PAPP-A в регуляции содержания ИФР-I, VEGF, активированных форм NF-kB и -субъединиц HIF-1 в тканях рака эндометрия.

We have examined for the first time the relationship between the expression of PAPP-A metalloproteinase and insulin-like growth factors (IGF-I, IGF-II, VEGF) and transcription factors (NF-κB, HIF-1) playing an important role in pathogenesis of cancer. We also demonstrated a positive association between the level of PAPP-A metalloproteinase and the level of growth (VEGF and IGF-I) and transcription factors (NF-κB p50, NF-κB p65, HIF-1α). The current findings suggest an important role of PAPP-A in regulation of bioavailability of IGF-I, VEGF, activated forms of NF-κB, and α-subunits of HIF-1 in endometrial tumors.

The study included 63 patients operated on for squamous cell lung cancer. Tissue fragments of the removed lung with the bronchus at a distance of 4–5 cm from the tumor were the material for histological examination. In order to evaluate the characteristics of the inflammatory response in different variants of degeneration, the presence of cells expressing Ki67, p53, bcl-2, CD138, CD117, CD68 and CD79α in the infiltrate of each variant of the degenerative changes was studied. The inflammatory cell infiltrate in squamous cell metaplasia was characterized by the presence of large number of proliferative cells and cells expressing p53 and bcl-2. In this case, intensity of stromal infiltration by plasma cells, mast cells and macrophages was decreased. Basal cell hyperplasia in the presence of squamous cell metaplasia was characterized by a large number of proliferative cells and leukocytes expressing p53 and bcl-2, large number of plasma cells and by the decrease in the number of macrophages. The character of inflammatory response in squamous cell metaplasia was the same and depended no on the fact whether squamous cell metaplasia was combined with basal cell hyperplasia and neoplasia or not. More pronounced infiltration in sites of squamous cell metaplasia by CD68+ macrophages in case of its combination with neoplasia was the only exception

Плоскоклеточный рак головы и шеи, кото-рый занимает шестое ранговое место в общей структуре онкологической заболеваемости и со-ставляет в среднем 18–20 %, относится к числу социально значимой онкологической патологии. Несмотря на то, что указанные новообразования относятся к опухолям наружной локализации, они характеризуются частой запущенностью, связанной с бессимптомным течением, выяв-УДК: 617.51/.53–006.6–092.18

Matrix metalloproteinases play an important role in degradation of connective tissue structural proteins and regulate function of biologically active molecules. There is currently no definitive understanding of regulation of matrix metalloproteinase expression and function in tumor tissue. We have studied expression of matrix metalloproteinases-1, -2 and -9 and molecules that regulate the expression in tumor tissue and surrounding stroma, and relationship between levels of matrix metalloproteinases, tissue metalloproteinase inhibitors, extracellular matrix metalloproteinase inducer and clinico-morphologic parameters characteristic of head and neck squamous-cell carcinomas. The study was made on 50 postoperative head and neck squamous-cell carcinoma specimens. Immunohistochemical approach was used to analyze expression of matrix metalloproteinases1, -2 and -9, tissue metalloproteinases-1 and -2 inhibitors and extracellular matrix metalloproteinase inducer. Expression of matrix metalloproteinases-1, -2 and -9 and tissue inhibitor of metalloproteinase 1 was higher in stroma than in tumor cells, while tissue inhibitor of metalloproteinase 1 and extracellular matrix metalloproteinase inducer were expressed mainly in malignant cells. There was a direct relationship between expression of extracellular matrix metalloproteinase inducer on tumor cells and stromal expression of matrix metalloproteinases2 and -9 which suggested a regulatory role of extracellular matrix metalloproteinase inducer locating on tumor cell surface in the expression by matrix metalloproteinase microenvironment. Expression of tissue metalloproteinase-2 inhibitor was decreased significantly in patients with regional lymph node disease. These results suggest that tissue metalloproteinase-2 inhibitor may be used as a potential prognostic marker.

A mathematical model based on principles of multifactor analysis was developed to predict clinical outcome of endometrial hyperplasia (EH) in patients with metabolic syndrome (80). Seventy-seven factors--anthropometric, clinical, anamnestic, hormono-metabolic, immunohistochemical, etc.--were included. Evaluation of the most informative indices integrated with the discriminative model showed that anthropometric (waist and hip circumference, sagittal diameter, etc.) and clinico-anamnestic (age, age of secondary sexual characters appearance, body weight at birth, suckling pattern, etc.) ones are of similar significance. A profile of hormono-metabolic parameters (cholesterol-low density lipoprotein, leptin, testosterone, progesterone and fasting glucose levels) helped identify a wide range of EH-related disorders in patients with metabolic syndrome. Consistently with the literature data, level of PTEN expression pointed to the presence of this tumor's suppressor in most EH cases which was matched by absence of its expression in endometrial carcinoma. Our model provided high sensitivity (89%) and specificity (82%) in predicting risk of progression in patients with endometrial hyperplasia and metabolic syndrome.

Multivariate analysis of data has yielded mathematical models of prognosis for endometrial cancer (EC) patients with and without metabolic syndrome (84 and 62 subjects, respectively). A total of 77 signs, including anthropometric, clinicoanamnestic, hormonal-metabolic, and immunohistochemical parameters, and the indicators of insulin-like growth factors in the endometrial tumors, were analyzed. All the patients with EC were divided into 2 groups in accordance with individual prognosis. The criteria for good prognosis were no recurrences, metastases, or death during 60 months. Analysis of the informative criteria included into the mathematical model indicated that EC patients with metabolic syndrome are typified by the fact that the formula contains values that are either direct criteria for metabolic syndrome or values closely clinically related to metabolic syndrome (insulin resistance, the level of triglycerides, and primary infertility). The specific feature of the model was an indicator, such as disease stage, for EC patients with metabolic syndrome and the histotype and differentiation degree of a tumor for those without metabolic syndrome, which seems to be associated with the fact that it is in this group that non-endometrioid tumors are much more frequently encountered. The level of PAPP-A was one of the most informative prognostic values in patients with and without metabolic syndrome.