Abstract
Introduction. There is evidence that disseminated tumor cells (DOCs) in the bone marrow (BM) are precursors of subsequent distant metastases. The detection of DOCs in non-small cell lung cancer (NSCLC) will provide important information about the features of metastasis, as well as the possibilities of identifying new targets for the treatment of NSCLC. Purpose of the study is to evaluate the possibility of detection DOCs in BM and to identify the frequency of BM involvement in patients with NSCLC. Materials and methods . Morphological and immunological methods studied 62 BM samples from patients with NSCLC. DOCs analysis was performed using flow cytometry (FACSCanto II, USA, Kaluza Analysis v 2.1 software), monoclonal antibodies to CD45, cytokeratins directly labeled with various fluorochromes were used. Results . DOCs (EPCAM+CD45–) in the BM were found in 43.5 % of patients (threshold level: 1 cell per 10 million myelocaricytes). The presence of DOCs did not correlate with tumor size, lymph node status, stage of the tumor process. The highest detection rates of DOCs were observed at stages IA and IIA: 60.7 % (3/5) and 58.3 % (7/12) respectively. BM involvement in adenocarcinoma was observed in 45 % (15/33) cases, in squamous cell carcinoma – in 37 % (10/27) samples (p = 0.501). It was found that DOCs are more often detected in more differentiated tumors (p = 0.023). Significant correlations between the presence of DOCs in the BM and myelogram parameters have not been established. A decrease in the number of granulocyte germ cells was observed in 4 % of BM involvement (p = 0.036). Conclusion. The possibility of detecting DOCs in the BM of NSCLC patients has been established. BM involvement was 43.5 %. DOCs are detected even in the early stages of NSCLC. Relationship between BM involvement and the degree of tumor differentiation was found. More frequent BM involvement was observed in adenocarcinoma compared with squamous cell carcinoma of the lung. Compliance with patient rights and principles of bioethics The study protocol was approved by the biomedical ethics committee of N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. All patients gave written informed consent to participate in the study.
Highlights
There is evidence that disseminated tumor cells (DOCs) in the bone marrow (BM) are precursors of subsequent distant metastases
Purpose of the study is to evaluate the possibility of detection DOCs in BM and to identify the frequency of BM involvement in patients with non-small cell lung cancer (NSCLC)
DOCs analysis was performed using flow cytometry (FACSCanto II, USA, Kaluza Analysis v 2.1 software), monoclonal antibodies to CD45, cytokeratins directly labeled with various fluorochromes were used
Summary
Существуют многочисленные подтверждения того, что при ряде опухолей диссеминированные опухолевые клетки (ДОК) в костном мозге (КМ) – предшественники последующих отдаленных метастазов. Цель исследования – оценить возможность детекции ДОК в КМ у больных НМРЛ, а также проанализировать частоту поражения и взаимосвязь с клинико-морфологическими параметрами опухоли. Наибольшая частота обнаружения ДОК наблюдалась при IА- и IIА-стадии и составила 60,7 % (3 / 5) и 58,3 % (7 / 12) соответственно. Поражение КМ в 45 % (15 / 33) случаев наблюдалось при аденокарциноме, при плоскоклеточном раке опухолевые клетки выявлены в 37 % (10 / 27) образцов (р = 0,501). Установлено, что ДОК чаще выявляются при более дифференцированных опухолях (р = 0,023). Установлена возможность детекции ДОК в КМ больных НМРЛ. В сравнении с плоскоклеточным раком легкого более частое поражение наблюдалось при аденокарциноме. Pirogov Russian National Research Medical University, Ministry of Health of Russia; 1 Ostrovitianov St., Moscow 117997, Russia; 3'2020 том 19 vol 19
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