Calcitonin as a biomarker of C cell disease: recent achievements and current challenges

The neoplastic proliferation of parafollicular thyroid cells (C cells) may occur as either medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) and is generically defined C cell disease. Since Calcitonin (CT) expression is fully maintained in neoplastic C cells, this hormone represents a sensitive marker for neoplasia of C cell derivation such as CCH and MTC. Serum CT levels display a high prognostic value and accurate estimation of tumor burden, allowing early detection of persistence/relapse and representing a reliable marker of response to treatment. Indeed, elevated CT levels can occur in other non-C cell-related conditions (i.e., other malignancies, systemic diseases, and pharmacological treatments). Moreover, some de-differentiated, more aggressive MTCs may present disproportionately low-circulating CT levels, as compared with tumor burden. During the postsurgical follow-up of MTC patients, CT levels usually parallel tumor progression and their increase unambiguously announces persistence/relapse. In this respect, CT Doubling Time (DT) has been proposed as prognostic factor of potential use for the identification of more aggressive MTCs. The present review will summarize the novel achievements on the clinical suitability of CT as a biomarker in clinical oncology and will point the attention to the most recent results concerning the usefulness and the possible drawbacks of circulating CT as a surrogate marker for the identification of rapidly progressing MTC patients, such as those candidate to targeted therapies. The emerging role of circulating CT as a parameter of response to local and systemic therapies will also be illustrated.