Disseminated tumor cells (DTCs) are studied as a prognostic factor in many non-hematopoietic tumors. Melanoma is one of the most aggressive tumors. Forty percent of melanoma patients develop distant metastases at five or more years after curative surgery, and frequent manifestations of melanoma without an identified primary lesion may reflect the tendency of melanoma cells to spread from indolent sites such as bone marrow (BM). The purpose of this work was to evaluate the possibility of detecting melanoma DTCs in BM based on the expression of a cytoplasmatic premelanocytic glycoprotein HMB-45 using flow cytometry, to estimate the influence of DTCs’ persistence in BM on hematopoiesis, to identify the frequency of BM involvement in patients with melanoma, and to analyze DTC subset composition in melanoma. DTCs are found in 57.4% of skin melanoma cases and in as many as 28.6% of stage I cases, which confirms the aggressive course even of localized disease. Significant differences in the groups with the presence of disseminated tumor cells (DTCs+) and the lack thereof (DTC−) are noted for blast cells, the total content of granulocyte cells, and oxyphilic normoblasts of erythroid raw cells.

Despite the fact that melanoma is a tumor of visual localization, mortality from skin melanoma remains one of the leading causes of mortality worldwide. Early metastasis of melanoma, even during the initial stages of the tumor process, indicates a high malignant potential of the tumor. Moreover, metastatic melanoma is resistant to current chemotherapy regimens, which is a significant problem today. Progression, resistance to drug therapy of skin melanoma is associated with a population of tumor stem cells, which are characterized by dysregulation of signaling pathways and aberrant phenotypes. The formation of tumor stem cells contributes to their microenvironment. Surface markers expressed by tumor stem cells include transporter proteins that mediate chemoresistance. The study of the microenvironment, the activity of the expressed antigenic determinants makes it possible to understand the processes of chemoresistance formation and to discover (develop) strategies for its overcoming. The article provides an analysis of the literature data on the significance of tumor stem cells in the development of drug resistance of melanoma.

Background. Melanoma of the skin is characterized by a rapid progression and early metastasis. It has been shown the disseminated tumor cells, which are often found in the bone marrow, has an important prognostic value. The study of disseminated tumor cells in melanoma might be one of the possible additional sources of information about the nature of the disease and potential application points for drug therapy. Aim. To study the frequency of detection of disseminated tumor cells in the bone marrow in melanoma, depending on the clinical and morphological characteristics of the tumor. Materials and methods. The study included 67 patients with a verified diagnosis of melanoma who were examined and treated at the Blokhin National Medical Research Center of Oncology from 2014 to 2019 years. Male patients accounted for 50.7% (n=34), female patients 49.3% (n=33). The average age of patients: 50.11.6 years. Immunological and morphological examination of the bone marrow were perfomed. Morphological examination was performed by two independent morphologists. Disseminated tumor cells were evaluated by flow cytometry among all nucleated cells (Syto41+) based on the expression of the HMB-45 antigen and the absence of expression of the CD45 panleukocyte antigen (FACS Canto II, USA, Kaluza Analysis v2.1). Statistical data processing was performed using the IBM-SPSS Statistics v.21 Results. Morphologically bone marrow damage was not detected in any case. Disseminated tumor cells (CD45-HMB-45+) in the bone marrow of melanoma patients were detected in 62.7% (n=42) of cases by flow cytometry. The frequency of bone marrow damage in the early stages is not lower than in advanced ones (p=0.029). This is clearly seen in the enlarged analysis. The percentage of DTC detection. At stages I and II was 60.0% (6/10) and 84.6% (11/13), respectively, at stages III and IV 44.4% (8/18) and 65.4% (17/26). In addition, the frequency of detection of disseminated tumor cells in the bone marrow was higher in young patients (p=0.02). There was no correlation between the frequency of bone marrow damage depending on BRAF status. Conclusion. The connection of disseminated tumor cells with the clinical and morphological characteristics of the melanoma has been established. Melanoma is characterized by frequent bone marrow damage, even in the early stages, in young patients.

No abstract