Bone Marrow Involvement in Melanoma. Potentials for Detection of Disseminated Tumor Cells and Characterization of Their Subsets by Flow Cytometry

Abstract

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.

Bone Marrow Lymphocyte Populations of Innate Immunity in Breast Cancer Patients

“…The study of hematopoiesis in patients with breast cancer revealed a number of patterns that we had noted in earlier studies with squamous cell carcinoma of the head and neck, melanoma, and also with lymphomas [12,13]. A decrease in the populations of basophilic and polychromatophilicnormoblasts and an increase in oxyphilic forms have been established.…”

“…A decrease in the populations of basophilic and polychromatophilicnormoblasts and an increase in oxyphilic forms have been established. It is important to note that such observations often occurred in cases of bone marrow involvement in the tumor process, for example, with melanoma [13]. In this study, we did not provide data on the presence of breast cancer micrometastases in the bone marrow; there was no lesion in all cases at the morphological level.…”

Detection of Disseminated Tumor Cells in the Bone Marrow of Patients With Non-Small Cell Lung Cancer

“…В настоящее время усилия ученых направлены на разработку различных стратегий повышения эффективности противоопухолевого иммунного ответа, и значительная доля научных исследований посвящена изучению иммунобиологических механизмов гематогенного метастазирования [2][3][4]. Предметом пристального внимания в этом контексте стали диссеминированные опухолевые клетки (ДОК), которые довольно часто обнаруживаются в костном мозге (КМ) онкологического больного [5][6][7][8]. Следует подчеркнуть, что практически у 40 % таких больных имеются ранние стадии опухолевого процесса.…”

“…Эти процессы приводят к приобретению ими новых фенотипических признаков. В недавней работе показана гетерогенность ДОК: они экспрессируют на своей поверхности разнообразный набор антигенов [7], что отличает их от первичной опухоли и отражает сложную архитектуру отношений между ДОК и микроокружением. Имеются данные, что ДОК в КМ могут иметь геномные профили, не связанные с первичной опухолью [13].…”

“Circulating Tumor Cells: Finding Rare Events for a Huge Knowledge of Cancer Dissemination”

“…Chernysheva et al studied disseminated tumor cells (DTCs) as a prognostic factor in many non-hematopoietic tumors [9]. They evaluated the possibility of detecting subsets of melanoma DTCs in the bone marrow based on the expression of a cytoplasmic premelanocytic glycoprotein HMB-45 using flow cytometry.…”