Detection of disseminated tumor cells in lymph nodes from patients with early stage non-small cell lung cancer

Abstract

BackgroundThe regional lymph node involvement is a major prognostic factor in patients with non-small cell lung cancer (NSCLC) undergoing surgical resection. Disease relapse is common, suggesting that early disseminated disease is already present in the regional lymph nodes at the time of surgery, and that the current nodal staging classification might be suboptimal. Early detection of disseminated tumor cells (DTCs) in lymph nodes could potentially enable identification of subcategories of patients with high risk of disease relapse.MethodLymph node samples were collected from 128 NSCLC patients at the time of surgery and the presence of DTCs determined by immunomagnetic selection (IMS) using the MOC31 antibody recognizing EpCAM. Results obtained with IMS were compared to the pathological staging obtained by histopathology. Associations between the presence of DTCs and clinicopathological variables and patient outcome were investigated.ResultsDTCs were detected in 40 % of the lymph node samples by IMS. Their presence was significantly associated with pN status as assessed by histopathology, and samples from 83 % of the patients with lymph node metastases (pN1-2) had detectable DTCs. In the group of patients who were negative for lymph node metastases by standard histopathology (pN0) DTCs were detected in 32 %. The presence of DTCs was not associated with any other clinicopathological variables. Patients with IMS-positive samples showed decreased relapse free survival compared to patients with IMS-negative samples, but the difference was not statistically significant. The pN status was significantly associated with both relapse free and overall survival, but the presence of DTCs had no prognostic impact in the subcategory of patients with pN0 status.ConclusionOur findings do not support further development of lymph node DTC detection for clinical use in early stage NSCLC.

Disseminated cancer cells detected by immunocytology in lymph nodes of NSCLC patients are highly prognostic and undergo parallel molecular evolution

“…The findings are consistent with reported prognostic relevance of minimal lymphatic spread in NSCLC patients using Ber-EP4 or antibodies against cytokeratins (AE1/AE3, CK5/6, CK7) for DCC detection [5][6][7][8][9][10][11][12][13][14]29]. Nevertheless, some studies report a lack of prognostic significance of DCCs or micrometastases [30][31][32], which may be related to the size of the patient cohort, patient selection biases, the length of follow-up, treatment effects, and the heterogeneity of the protocols used for detection of DCCs. Indeed, our data indicate that the low sensitivity of limited HP may blur true and false-negative cases, precluding clear separation of patients with and without local spread.…”

“…Possibly, a number of LNs can be determined that optimizes the balance between diagnostic precision and workload. Nevertheless, there is an imperative need to collect more information on the survival impact of DCCs, because several studies failed to demonstrate a significant effect of LN-DCC detection [30][31][32]. It needs to be determined whether the heterogeneity of detection methods or the use of different detection markers contributed to these conflicting results.…”

Radiation therapy-induced metastasis: radiobiology and clinical implications

“…Many patients succumb to distant metastases despite optimal loco-regional control of primary lesions (Figure 2), primarily attributed to so-called occult micro-metastases which were already present at the time of diagnosis [42][43][44]), with subsequent growth at these distant sites appearing once a supportive vascular network is established.…”

Genetic Clonality as the Hallmark Driving Evolution of Non-Small Cell Lung Cancer

“…Therefore, lymph node metastases are often detected simultaneously with primary tumor [ 17 , 115 , 116 ]. This confirms that lymph node metastases are seeded a long before clinical detection and, at that moment, they do not contribute to migration to other sites; however, they evolve in parallel with primary tumors sharping the genetic divergence [ 116 , 122 ]. Primary NSCLC, and its corresponding lymph node metastases, present high concordance in clonal alterations, indicating that local metastases may arise from the major clone of primary tumor [ 114 , 123 ].…”