20 years of RET/PTC in thyroid cancer: clinico-pathological correlations

The RET/PTC oncogene has been isolated almost twenty years ago. During these years, the research has given a final answer to several questions. In fact, it has been demonstrated that: a) RET/PTC is an early event in the process of thyroid carcinogenesis and has a critical role in the generation of the papillary carcinoma; b) RET/PTC activation is essentially restricted to the papillary histotype and to the Hürthle thyroid tumors; c) its incidence increases after exposure to radiations. However, some questions have not found a final answer yet: a) which is the real frequency of RET/PTC activation? Likely it is around 20%, but this point is still questionable; b) which other gene modifications are required to lead a thyroid cell carrying a RET/PTC oncogene to the malignant phenotype?, and c) is there any correlation between RET/PTC activation and clinical parameters? We hope that these questions will have a clear answer in the near future.