[Fetal cell carcinogenesis hypothesis and its impact on clinical pathology of cancer]

Since the 1980s, cancer cells have been considered to be derived from well-differentiated normal cells via multiple incidents of damage to their genome, especially in oncogenes or tumor suppressor genes, which accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs. In the thyroid, a novel hypothesis of carcinogenesis, the "fetal cell carcinogenesis" hypothesis, in which thyroid cancer cells are derived from the remnants of fetal cells, instead of well-differentiated somatic cells, such as thyrocytes, by de-differentiation, is proposed. In this hypothesis, thyroid cancer cells are generated from three types of fetal thyroid cells, thyroid stem cells(TSCs), thyroblasts and prothyrocytes by proliferation without differentiation, which results in anaplastic, papillary and follicular carcinoma, respectively. Genomic alternations, such as RET/PTC and PAX8-PPARgamma1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. This hypothesis well explains the clinical and biological features and recent molecular evidence of thyroid cancer. Further, it underscores the importance of identifying stem cells and clarifying the molecular mechanism of organ development. Such data will lead to better understanding of thyroid carcinogenesis and the establishment of more accurate diagnostic methods and more effective therapies. Analysis of molecular behavior in a single tumor cell will be a key technology in the future clinical pathology. Fetal cell science may be the leading research theme in the next few decades.