Follicular cell-derived and medullary thyroid carcinomas constitute a biological continuum progressing from the highly curable well-differentiated forms to the rare aggressive and undifferentiated forms. A progressive dedifferentiation translates in a more aggressive tumor behavior and worse prognosis especially in patients with locally advanced or metastatic disease. Even if biosynthesis and secretion of thyroglobulin and calcitonin are partially retained in dedifferentiating follicular and parafollicular cells, the synthesis and secretion rate is reduced (i.e., poor secretors) in comparison to normal cells and differentiated cancer cells. Consequently, a large dedifferentiated tumor mass could be associated to low levels of circulating thyroglobulin and calcitonin, and, consequently, the role of these serum markers is rather limited in this scenario. Therefore, new circulating biomarkers are warranted to help identify patients most likely to benefit from these therapies. Recently, among a series of candidate tumor markers, carbohydrate antigen 19-9 (CA 19-9) and cytokeratin fragments 19 (Cyfra 21.1) emerged as potentially useful prognostic predictors in advanced differentiated thyroid carcinoma and medullary thyroid carcinoma, respectively. Biology and physiopathology, assay methods and laboratory pitfalls, current clinical data, and potential applications of such tumor markers will be addressed in the present chapter.
