Tumor cells may circulate in medullary thyroid cancer patients independently of serum calcitonin

in Endocrine-Related Cancer
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Dear Editor,

Early detection of tumor relapse is a major issue in patients with medullary thyroid carcinoma. Calcitonin has been reported as a sensitive and accurate marker for recurrence of medullary thyroid carcinoma after thyroidectomy. Recent evidence nevertheless reveals pitfalls in calcitonin immunoassays due to the presence of heterophilic antibodies or macroaggregates (i.e. falsely increased values or macrocalcitonin) (Alves et al. 2016). Calcitonin can also remain undetectable despite metastasis of rare tumor cells in thyroidectomized patients. In this context, we designed a sensitive and specific technique to identify calcitonin-positive circulating tumor cells (CTC) in medullary thyroid

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    (A) Representative results of CTCs identified using the CellSearch system (Veridex). CTCs were isolated with an EpCAM antibody and labeled for cytokeratin (CK), nuclei (DAPI) and leukocyte common antigen (CD45) as described in the Supplementary data. (B) Summary of CTC counts in thyroid cancer, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). The numbers and percentages of patients without CTC (0), with one or with more than one are indicated. (C) The TT cell line derived from medullary thyroid carcinoma was labeled with SP17 anti-calcitonin antibody and visualized by fluorescence microscopy. (D) CTCs were isolated by size of epithelial tumor cells (ScreenCell device) from peripheral blood of a patient with medullary thyroid cancer. Cells were labeled and visualized as described in panel B. Arrows indicate calcitonin-positive CTCs (green) and their nuclei (DAPI in blue). (E) The number of calcitonin-positive CTCs was plotted against the concentration of serum calcitonin (pg/mL). R2 is the correlation coefficient.

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