Prognostic relevance of circulating tumor cells in blood and disseminated tumor cells in bone marrow of patients with squamous cell carcinoma of the oral cavity
Menée sur 110 patients atteints d'un carcinome épidermoïde de la cavité buccale traité par résection, cette étude évalue, du point de vue de la survie sans récidive, la valeur pronostique des cellules tumorales circulantes et des cellules tumorales disséminées dans la moelle osseuse
PURPOSE: Current staging methods for squamous cell carcinomas of the oral cavity (OSCC) need to be improved to predict the risk of individual patients. Since hematogenous tumor cell dissemination is a key event in tumor progression we assessed the prognostic significance of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTCs) in peripheral blood (PB) from OSCC patients. EXPERIMENTAL DESIGN: From 110 patients with OSCC, tumors were surgically resected (R0) without neoadjuvant therapy. The CellSearch™-system was used to enumerate CTCs. BM was aspirated from the iliac crest, and mononuclear cells (MNCs) were enriched by Ficoll density gradient centrifugation. To detect DTCs, MNCs were immunostained with the pan-keratin antibody A45-B/B3. Results were correlated with clinicopathological parameters and clinical outcome such as recurrence and death during follow up time (mean 916 days). RESULTS: Ten/80 patients (12.5%) harbored CTCs in PB whereas in 18/90 patients (20.0%) DTCs in BM could be detected. Surprisingly, in only two patients (1.8%) CTCs and DTCs were detected simultaneously. Significant correlations could be found regarding CTCs and tumor size (p=0.04), nodal status and DTCs (p=0.02), and distant metastasis with CTCs (p=0.004) and DTCs (p=0.005). Univariate and multivariate analyses revealed that CTCs and DTCs were significant and independent predictors of recurrence-free survival (p<0.001). CONCLUSIONS: Both DTCs and CTCs are independent prognostic markers in OSCC patients, predicting relapse with higher sensitivity at various disease stages than routine staging procedures. Bone marrow might be an interesting target organ for future therapeutic interventions.
Clinical Cancer Research , résumé, 2013