IDENTIFICAZIONE DI CELLULE TIROIDEE MALIGNE CIRCOLANTI. POTENZIALE UTILIZZO NEL FOLLOW-UP DEL PAZIENTE CON CARCINOMA DELLA TIROIDE.

DESIGN: The follow-up program of patients with Differentiated Thyroid Cancer (DTC) is based on the evaluation of serum thyroglobulin (Tg) levels in different conditions, associated with the neck ultrasonography and, occasionally, with other imaging techniques. Nevertheless, in a part of patients, particularly those with poorly differentiated cancers, Tg evaluation has lower sensitivity. In these cases, the availability of alternative diagnostic methods would be important. In the last years a new diagnostic tool has been proposed, based on the identification of Circulating Tumor Cells (CTCs) through immunomagnetic assay (CellSearch System®), cytofluorimetric methods and molecular biology analysis. The aim of our study was to identify thyroid CTCs in patients with DTC underwent both thyroidectomy and radioiodine (131-I) remnant ablation (RAI) and to assess the possible role of CTCs in the follow-up. METHODS: A total of 22 patients with DTC treated by thyroidectomy + RAI were retrospectively studied. Seventeen out of 22 had detectable serum Tg concentrations (persistent/reccurrent disease), 5 out of 22 had undetectable stimulated Tg levels (cured), whereas 6 out of 22 were healthy volunteers. In all patients CTCs were assessed by both CellSearch® System and multichannel cytofluorimetric assay. Thyroid CTCs were confirmed by RT-PCR for Tg-mRNA. As CellSearch® System is concerned, only CTCs with immunophenotype EpCAM(+)/Cytokeratin(+)/CD45(-)/DAPI(+) were counted, whereas the pattern TSHR-PE+/CD45- was employed to identify thyroid circulating cells by cytofluorimetric method. RESULTS: CTCs were observed in 65% of DTC patients with persistent disease, and in 0% of cured patients. Thyroid phenotype of CTCs was confirmed in 90% of samples by RT-PCR for Tg-mRNA. Levels of circulating thyroid cells detected by the cytofluorimetric method were higher in DTC patients with persistent disease than in cured patients, as well as in the healthy volunteer subjects. CONCLUSION: Thyroid CTC identification by CellSearch® System is a very specific method to identify thyroid cancer recurrence, but the low sensitivity doesn't yet allow the clinical use. With regards to the cytofluorimetric method, the number of events TSHR+/CD45- is higher in patients with persistent disease than in the other groups, althought with a significant overlap of the data. The lack of statistical correlation between CTCs and histotype, TNM, basal serum Tg levels, RAI dose and metastatic localizations, may suggest that CTCs could represent a different cell population, with a possible precursor role. At the present state of our knowledge, our data suggest that CTCs detection can not represent an alternative tool to the serum Tg level evaluation in the follow up of patients with differentiated thyroid carcinoma.