Minor role of TP53and TERTpromoter mutations in medullary thyroid carcinoma: report of new cases and revision of the literature

Purpose: Aims of this study were to investigate the prevalence of TP53and TERTmutations in Medullary Thyroid carcinoma (MTC) and their role in inducing aggressiveness in positive cases. Methods: We performed a literature search in PubMed to identify studies investigating the prevalence of TERTand TP53mutations in MTC. We also included data on MTC cases (n = 193) obtained at our center and unpublished. The in-silico pathogenicity of the TP53mutations has been evaluated by predictor tools. Results: We identified a total of 25 and 11 published papers: all together 1280 cases have been investigated for the presence of TP53mutations and 974 for TERTpromoter mutation. Twenty-five out of 1280 (2%) cases had a TP53mutation while only 3/974 MTC cases (0.3%) have been found to be positive for TERTpromoter mutations. Among all, we identified 19 different TP53 mutations that in 12 cases were demonstrated to have an in silico predicted high pathogenic role and a high impact on protein function. Three non-sense and 4 probably not damaging mutations were also reported. The pathogenic role of the TERTpromoter mutations has been previously in vitro determined. No correlation between TP53and/or TERTmutations and aggressiveness of MTC has been demonstrated. Conclusion: The prevalence of TP53and TERTpromoter mutations is very low in MTC. The reported mutations are pathogenic in the majority of cases. Because of their rarity it is not possible to clarify if they play or not a role in the pathogenesis and/or aggressiveness of this specific thyroid tumor.