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.
OBJECTIVE
Current staging methods for squamous cell carcinomas (SCC) of the oral cavity (OSCC) need to be improved to predict the risk of individual patients. Because hematogenous tumor cell dissemination is a key event in tumor progression, we assessed the prognostic significance of disseminated tumor cells (DTC) in bone marrow and circulating tumor cells (CTC) in peripheral blood from patients with OSCC.


METHODS
From 110 patients with OSCC, tumors were surgically resected (R0) without neoadjuvant therapy. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest, and mononuclear cells (MNC) 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 clinicopathologic parameters and clinical outcome such as recurrence and death during follow-up time (mean 916 days).


RESULTS
Ten of 80 patients (12.5%) harbored CTCs in peripheral blood, whereas in 18 of 90 patients (20.0%) DTCs in bone marrow could be detected. Surprisingly, in only 2 patients (1.8%) CTCs and DTCs were detected simultaneously. Significant correlations could be found for 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 patients with OSCC, 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.
Authors' Affiliations: Departments of Oral and Maxillofacial Surgery, Medical Biometry and Epidemiology, and Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Alexander
A
Gröbe
Marco
M
Blessmann
Henning
H
Hanken
Reinhard E
RE
Friedrich
Gerhard
G
Schön
Johannes
J
Wikner
Katharina E
KE
Effenberger
Lan
L
Kluwe
Max
M
Heiland
Klaus
K
Pantel
Sabine
S
Riethdorf
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D019046:Bone Marrow Neoplasms / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012008:Recurrence; D047368:Tumor Burden