Bone Marrow Involvement in Non-Small Cell Lung Cancer

Abstract

Disseminated tumor cells (DTCs) in the bone marrow (BM) have been shown to be progenitors to distant metastases. The discovery of DTCs in non-small cell lung cancer (NSCLC) will provide crucial information on the characteristics of metastasis, as well as the potential for discovering new targets for NSCLC treatment. The goal of the study is to see if DTC can be detected in BM and to determine the incidence of BM involvement in NSCLC patients, as well as their impact on the BM lymphocyte population. Morphological and immunological approaches were used to examine 62 bone marrow samples from NSCLC patients. DTCs analysis was performed using flow cytometry (FACS Canto II, the USA, Kaluza Analysis v2.1 software), monoclonal antibodies to CD45, EPCAM, CD133, lymphocyte populations CD3, CD4, CD8, CD19, CD20, CD16, CD27, directly labeled with various fluorochromes were used. The EPCAM+CD45- (DTCs) in the BM were found in 43.5% of patients (threshold level: 1 cell per 10 million myelocaricytes). The CD133+EPCAM+CD45-cells were found in 33,3% (9/27) cases. The presence of DTCs had no relationship to tumour size, lymph node status, or tumour stage. DTCs were detected at the highest rates in stages IA and IIA: 60.7 percent and 58.3 percent, respectively. In adenocarcinoma, BM involvement was found in 45 percent of cases, while in squamous cell carcinoma, it was found in 37 percent of samples (p = 0.501).  DTCs were observed to be more common in highly differentiated tumours (p = 0.023). There are no significant connections between the presence of DTCs in the BM and myelogram parameters. A decrease in the number of granulocytic lineage cells was observed in 4% of BM involvement (p = 0.036). A significant increase in the level of subpopulations of CD16 + CD4-NK-cells (p = 0.002), CD27 + CD3 + T-cells (p = 0.015) with BM damage was revealed. Conclusion: It has been proven that DTCs can be detected in the BM of NSCLC patients.43.5 percent of the participants were from the BM. Even in the early stages of NSCLC, DTCs are found. There was a link discovered between BM involvement and the degree of tumour differentiation. Adenocarcinoma of the lung had a higher rate of BM involvement than squamous cell carcinoma of the lung. A relationship between DTCs and BM lymphocyte populations was revealed: subpopulations of CD16 + CD4-, CD27 + CD3+.