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Bone marrow involvement in non-small cell lung cancer: Detection of disseminated tumor cells and cancer stem cells.

SV Chulkova, NN Tupitsyn

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, as well as their effect on the population of bone marrow lymphocytes.
Materials and methods: 62 bone BM of NSCLC patients were studied by morphological and immunological methods. Doc’s analysis was performed using flow cytometry (FACS Canto II, USA, Kaluza Analysis v2.1 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 CD133 expression was found (CD133+EPCAM+CD45-) in 33.3% (9/27) cases. The presence of DOCs did not correlate with tumor size, lymph node status and stage of the tumor process. The highest detection rates of DOCs were observed at stages IA and IIA: 60.7% and 58.3% respectively. BM involvement in adenocarcinoma was observed in 45% cases, in squamous cell carcinoma - in 37% 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.