Circulating epithelial cells in patients with thyroid carcinoma

Summary

Goal: To investigate whether circulating epithelial cells (CEC) recognized via the epithelial cell adhesion molecule (EpCAM) can be identified in the blood of patients with thyroid carcinoma, given that CEC have already been detected in other types of carcinoma and are considered a potential marker of tumour dissemination. Patients, methods: Blood samples of patients with active differentiated thyroid carcinoma (DTC) (n = 50) were compared to samples of patients with: a) recent surgical excision of a thyroid carcinoma (postOP-DTC) (n = 16); b) athyreotic, tumour-free status after radioiodine ablation (AT-DTC) (n= 33); and c) benign thyroid diseases (BTD) (n = 51). Samples of volunteers with normal thyroid parameters (NT) (n = 12) were also investigated. Cells from EDTAblood were subjected to erythrocyte lysis, isolated by centrifugation, and incubated with a fluorescence-labeled antibody against EpCAM. The numbers of vital cells were counted via fluorescence microscopy. Results: CEC were identified in all groups, with the postOP-DTC group showing the highest mean CEC numbers of all groups. The DTC group had significantly higher CEC numbers than the NT group, and numerically higher numbers than the other groups, although not reaching statistical significance. Within the DTC group there was a correlation between levels of serum thyroglobulin and numbers of CEC (r = 0.409, p = 0.003). Conclusions: High CEC numbers were not specific to thyroid carcinoma. The methodology used here, based on a single measurement does not allow to identify severe forms of DTC, emphasizing the need of longitudinal measurements throughout therapy. Detection and characterization of tumour thyroid cells in circulation should be based on additiona l consideration of tissue-specific characteristics.

Zusammenfassung

Ziel: Zu untersuchen, ob sich im Blut von Patienten mit differenziertem Schilddrüsenkarzinom (DTC) EpCAM(Epithelial Cell Adhesion Molecule)-positive Zellen (Circulating Epithelial Cells, CEC) befinden. CEC wurden bei verschiedenen Karzinomen nachgewiesen und werden als potenzieller Marker der Tumorzellaussaat angesehen. Patienten, Methodik: Blutproben von Patienten mit DTC (n = 50) wurden mit Proben von a) Patienten mit kürzlich erfolgter Thyreoidektomie aufgrund eines DTC (post-OP DTC) (n = 16); b) athyreoten, geheilten DTC-Patienten nach Radiojodablation (AT-DTC) (n = 33); c) Patienten mit gutartigen Schilddrüsenerkrankungen (BTD) (n = 51) verglichen. Außerdem wurde eine Kontrollgruppe ohne Schilddrüsenpathologien untersucht (NT) (n = 12). CEC wurden aus EDTA-Blut durch Erythrozytenlyse und Zentrifugation isoliert, anschließend mit einem fluoreszenzmarkierten Anti-EpCAM-Antikörper inkubiert und die Anzahl der CEC mit Fluoreszenzmikroskopie ermittelt. Ergebnisse: CEC wurden in allen Gruppen nachgewiesen. Die höchsten Werte zeigte die postOPDTC-Gruppe. Die DTC-Gruppe wies signifikant höhere CEC-Mittelwerte auf als die NTGruppe und ebenfalls mehr CEC als andere Gruppen (nicht signifikant). In der DTC-Gruppe war eine Korrelation zwischen CEC und Serumthyreoglobulinkonzentration vorhanden (r = 0.409, p = 0.003). Schlussfolgerung: Der Nachweis einer erhöhten Anzahl an CEC ist nicht schilddrüsenkarzinomspezifisch. Die hier angewandte Methode einer CECMessung lässt es nicht zu, komplizierte DTCVerläufe zu erfassen. Deshalb ist die sequenzielle Messung der CEC unter einer Therapie notwendig. Außerdem sollte die Detektion von zirkulierenden Schilddrüsenkarzinomzellen unter dem Aspekt gewebsspezifischer Merkmale erfolgen.

Keywords

Differentiated thyroid carcinoma - circulating epithelial cells - EpCAM - CEC

Schlüsselwörter

Differenziertes Schilddrüsenkarzinom - zirkulierende epitheliale Zellen - EpCAM - CEC

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