Identification of Molecular Markers Altered During Transformation of Differentiated Into Anaplastic Thyroid Carcinoma

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Abstract
Transformation is a term commonly used to describe the biological process in which normal or premalignant cells undergo a change and become cancerous.1 For thyroid cancer, transformation or anaplastic transformation describes an intratumoral evolution, or progression, from differentiated thyroid cancer (DTC) into anaplastic thyroid carcinoma (ATC).2 Differentiated thyroid cancer, which includes papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), accounts for more than 90% of newly diagnosed thyroid malignancies, and with current treatment few individuals die of their disease.3 Even individuals who present with evidence of metastatic DTC can experience long-term survival.4 In contrast, ATC is considered one of the most lethal of all human cancers but accounts for less than 2% of all newly diagnosed thyroid malignancies.5 Despite advances in the understanding and treatment of human cancer gleaned during the past several decades, little improvement has occurred in the outcomes of individuals diagnosed as having ATC.6-8 Individuals diagnosed as having ATC tend to present with a rapidly enlarging symptomatic neck mass, and many have evidence of metastatic disease.6-8 A report that evaluated the outcome of 516 patients with ATC from the National Cancer Institute's Surveillance, Epidemiology, and End Results database found that at presentation 38% of newly diagnosed ATC cases had evidence of either extrathyroidal tumor extension or lymph node invasion and 43% of cases had distant metastasis.9 The observed overall cause-specific mortality of this ATC cohort was 68.4% at 6 months and 80.7% at 12 months.9 Death from ATC is caused by either local and/or regional disease extension, which leads to suffocation or multiorgan failure as a consequence of overwhelming distant metastatic disease.6-8 In selected patients with ATC who are able to tolerate aggressive multimodal treatment protocols, local disease may be controlled and death occurs as a consequence of distant metastases.10,11

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