Increased Numbers of Circulating Tumor Cells in Thyroid Cancer Patients

Abstract

Circulating tumor cells (CTCs) have been shown to be a valuable prognostic marker for different solid cancers. Within the present study we quantified CTCs in thyroid cancer (TC) patients. Special focus was given to disease-free PTC patients with undetectable serum thyroglobulin (Tg) levels. Altogether, 67 TC patients (33 papillary, 20 follicular, 14 medullary) were included in the study. CTC numbers, which were normalized to 3.3×10 peripheral blood mononuclear cells, were correlated with clinical outcome. TC patients had significantly higher CTC numbers compared to controls. The number of CTCs correlated to the initial tumor stage. Importantly, in comparison to controls, differentiated TC patients with serum Tg levels<0.3 ng/ml (no evidence of tumor recurrence) revealed a significantly higher amount of CTCs, also associated to their former tumor stage. Regarding the tumor-free papillary TC (PTC) patients the number of CTCs additionally correlated to the time point of radioiodine (RI) therapy: PTC patients with RI therapies>8 years before CTC measurement had significantly higher CTC numbers compared to those with RI therapy<8 years ago. We found a clear correlation between the number of CTCs and the tumor stage. Importantly, PTC patients who are in remission may still have increased numbers of CTCs. Follow-up analyses in these patients will reveal whether these data will have a clinical impact.

BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer

“…Differences in response rates could be explained by varying expression of retinoid receptors [22,25]. Usually, high Tg levels after thyroidectomy and RIT mark tumor recurrence [2,22,26]. However, several studies indicate that Tg levels could increase either because of tumor redifferentiation or tumor cell destruction [20,22,26].…”

“…Papillary thyroid cancer (PTC) is the most common neoplasia in the thyroid gland [1]. The combination of surgery, followed by radioiodine therapy (RIT) and thyroid-stimulating hormone (TSH) suppres-sive therapy is usually a curative option for differentiated thyroid cancer (DTC), which makes up over 90 % of all thyroid tumors [2]. However, 7-23 % of these patients develop distant metastases and two-thirds of those become refractory to radioiodine (RAI-R), decreasing the 10-year survival rate to 10 % [3,4].…”

Current progress in the clinical use of circulating tumor cells as prognostic biomarkers

“…69 In patients with thyroid cancer, CTCs have been associated with cases in which tumors were resected at an advanced stage, and also tend to increase significantly after radiotherapy. 70 CTCs currently are being explored for disease monitoring and prognostication, in particular for predicting metastasis and iodine-131 treatment response. 71 Using new techniques, CTCs have been shown to be useful in both prognosis and in characterizing clinicopathological features in patients with thyroid cancer.…”

“…In patients with thyroid cancer, CTCs have been associated with cases in which tumors were resected at an advanced stage, and also tend to increase significantly after radiotherapy . CTCs currently are being explored for disease monitoring and prognostication, in particular for predicting metastasis and iodine‐131 treatment response .…”

Current and future markers for the diagnosis of thyroid cancer

“…In this context, increasing number of studies had evaluated immunohistochemical markers, such galectin-3, CK19, HBME-1, TPO; DNA alterations, mainly including BRAF and RAS point mutations, RET/PTC and PAX8/PPARg rearrangements; miRNA signatures and circulating tumor cells for diagnosis of thyroid cancers [4][5][6][8][9][10][11][12]. While some markers are promising for differential diagnosis, none of them is individually conclusive because of limitations due to significant prevalence in benign thyroid nodules to a notable extent.…”