The aim of the study was to create a patient-derived xenograft (PDX) model of human colorectal cancer and to determine its histologic and molecular characteristics, such as the status of KRAS, NRAS, and BRAF genes and the presence of microsatellite instability.Materials and methods. First generation xenograft models in vivo were created using tumors from patients with colorectal cancer (n = 4) and immunodeficient Balb/c Nude mice (n = 20); second, third, and fourth generation models were created in the same mouse line (n = 3 for each generation). A caliper was used to measure subcutaneous xenografts; their size was calculated by the ellipsoid formula. Cryopreservation involved immersing the samples in a freezing medium (80% RPMI 1640, 10% fetal bovine serum, 10% dimethyl sulfoxide (DMSO)) and storing them at –80 °C. The histologic analysis was performed according to the standard technique (preparation of paraffin blocks and staining of microsections with hematoxylin and eosin). Mutations in the KRAS, NRAS, and BRAF genes were determined by direct Sanger sequencing; microsatellite instability was determined by the fragment analysis at five loci: Bat-25, Bat-26, NR21, NR24, and NR27.Results. Stable, transplantable xenografts of colorectal cancer were obtained from two out of four patients. The average waiting time from the implantation to the growth of the first generation xenograft was 28 days. The latency phase after cryopreservation was comparable to that at the creation of the first generation PDX model. The model reproduced the histotype, grade and mutational status of the KRAS, NRAS, and BRAF genes, as well as microsatellite instability of the donor tumor.Conclusion. The developed model of human colorectal cancer was characterized in terms of growth dynamics, cryopreservation tolerance, and histologic and molecular genetic parameters.

Background. The progression of malignant tumors, including vulvar cancer, largely depends on the state of the extracellular matrix and immune microenvironment of the tumor, the study of which is an urgent problem of oncology to identify the most prognostically significant of them. Aim. To evaluate the expression of extracellular matrix and local immunity factors, as well as their relationships in vulvar cancer with different prevalence. Material and methods. A retrospective study on vulvar tumors in 56 patients with stage I (n=20), stage II (n=26) and relapses (n=10) was performed. The expression of markers of the extracellular matrix (matrix metalloproteinases MMP-2 and MMP-9, tissue inhibitor of metalloproteinase-2 TIMP-2) and local immunity (FOXP3, CD68, CD206) was determined by immunohistochemical method. Statistical processing was performed using the MannWhitney U-test and multiple correlation analysis with the calculation of paired and partial R coefficients. Results. The depth of invasion proved to be more informative for detecting multidirectional differences in the expression of MMP-2 and TIMP-2 than the stage. Infiltration by CD68+-macrophages in the stroma increased in parallel with the stage and did not differ at different depths of invasion; infiltration by macrophages M2 (CD206+) increased at stage II compared with stage I (Me 13 and 5, respectively, p=0.03). Differences were noted only in the stroma of tumors, as well as an increase in T-regs (FOXP3) with an increase in the depth of invasion (Me 25 and 8, respectively, p=0.0359). As the prevalence of the tumor developed, the number of correlation relationships between the parameters of local immunity of the parenchyma and tumor stroma increased: 2 statistically significant correlations that do not depend on covariates, 7 that depend on the stage, and 6 that depend on the depth of invasion, were found. Correlations of factors of the immune microenvironment with the extracellular matrix weakened. Conclusion. The levels of MMP-2, TIMP-2, CD68+, CD206+, FOXP3 reflect the progression of vulvar cancer and can be used to predict the course of the disease; infiltration of tumors by macrophages, T-regs characterizes the stage of the primary tumor rather than recurrence.

November 4, 2020, marks the 100th anniversary of the birth of Oleg Konstantinovich Khmelnitskiy, an outstanding Russian pathologist, Corresponding Member of the Russian Academy of Medical Sciences (04.11.192008.02.2004). The creative legacy of O.K. Khmelnitskiy has a large number of works devoted to endometrial cancer and neuroendocrine tumors. Modern concepts of these tumors take a lot from the scientists ideas. The development of the classification of endometrioid carcinomas is determined by new data in molecular genetic research. The most common genetic changes in endometrioid adenocarcinomas involve mutations in the PTEN, KRAS, CTNNB1, PIK3CA, and MS1 genes. Serous carcinomas are characterized by TP53 mutations and HER2-neu gene amplification. The immunohistochemical panel allows differentiation of endometrioid and serous carcinomas. There is evidence of the role of the POLE gene mutation. Various advantages of the introduction of molecular genetic classification are presented, which allow changing approaches to the treatment of endometrial cancer depending on the risk of its development. The 2019 neuroendocrine tumors (NETs) classification allows interpreting morphological characteristics of these tumors in a new way.

The modern concept of general carcinogenesis is built on the basic knowledge of exogenous and endogenous factors. They change the body–organ–cell homeostatic and tissue basis and lead to genetic and molecular alterations followed by uncontrolled abnormal cell growth. We studied hepatocellular carcinoma (HCC) as an example of malignant neoplasm carcinogenesis. The article presents some major molecular and genetic alterations resulting in HCC as well as their association with immune microenvironment that mostly determines the onset and further tumor development. These are morphological, molecular, and genetic factors on which the HCC classification we propose is based. It involves 2 tumor classes (proliferating and nonproliferating) and will enable for determining the upcoming prospects for diagnosis of and treatment for this condition. Keywords: exogenous and endogenous risk factors, molecular and genetic and structural liver alterations, classification of hepatocellular carcinoma