To the editor:
In their paper in the January issue entitled 'Isolation of amniotic stem cell lines with potential for therapy', De Coppi et al.1 claim that embryonic stem (ES) cells “grow as teratocarcinomas when implanted in vivo.” This disagrees both with standard histopathological classification of germ cell neoplasms and with terminology previously used in the field to define ES cell–derived tissues.
Historically, the term teratocarcinoma has been used by pathologists to specifically define a malignant testicular germ cell tumor that is composed of teratoma and embryonal carcinoma. This neoplasm is associated with a malignant phenotype2,3, including the potential for distant metastasis4, local invasion and marked cytogenetic defects, as well as serial transplantability in experimental systems5,6,7. Teratocarcinomas are malignant tumors and may cause death due to invasion and metastasis if left untreated.
A more correct term for the experimental tissue masses formed by human ES cells is mature teratomas. Mature teratomas and ES cell–derived teratoma-like masses contain differentiated derivatives of all three embryonic germ layers and differ from teratocarcinomas in that they are considered benign2,6,8, do not invade adjacent tissues or metastasize to distant organs and typically do not reoccur after surgical removal9,10. Owing to their developmental potency, ES cell–derived masses that form in immunodeficient animals are referred to as teratomas by most other authors in the field11. That said, to a purist, neither term is correct, as both teratocarcinomas and teratomas are naturally occurring neoplasms that arise as a result of specific, acquired genetic and epigenetic alterations.
In contrast, experimental human ES cell–based 'lumps' result from disorganized but normal tissue generation and are a manifestation of a failed attempt, resulting from ectopic implantation, to form an embryo by ES cells that are genetically normal. Referring to the ES cell–derived tissue masses as teratocarcinomas (neoplastic tumors) is not only ontologically inaccurate: in view of the heated debate surrounding the conduct of human ES cell research, failing to make this important distinction could also have political implications.
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Lensch, M., Ince, T. The terminology of teratocarcinomas and teratomas. Nat Biotechnol 25, 1211 (2007). https://doi.org/10.1038/nbt1107-1211a
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