January 19, 2017
Frequency of Thyroid Carcinoma in Brazilian TP53 p.R337H Carriers With Li Fraumeni Syndrome
Maria Nirvana da Cruz Formiga, MD1; Kelvin César de Andrade, MSc2; Luiz Paulo Kowalski, MD, PhD3; et al
JAMA Oncol. Published online January 19, 2017. doi:10.1001/jamaoncol.2016.6389
Question Is thyroid carcinoma related to Li Fraumeni syndrome?
Findings In this cohort of 193 Brazilian patients with Li Fraumeni syndrome carrying the founder TP53 p.R337H mutation, thyroid carcinoma was observed in 11 of 101 cancer-affected patients.
Meaning Thyroid carcinoma is a frequent cancer in TP53 p.R337H mutation carriers, suggesting the need to include thyroid imaging in Li Fraumeni syndrome screening protocol.
Importance Li Fraumeni syndrome (LFS) is associated with a wide variety of tumors; nevertheless, thyroid carcinoma has not been evaluated in this syndrome. Due to the Brazilian founder mutation p.R337H, some tumors that have not been described in the classic LFS have been observed in a higher-than-expected prevalence in Brazil.
Objective To determine the frequency of thyroid carcinoma in Brazilian carriers of a founder TP53 p.R337H mutation.
Design, Setting, and Participants We reviewed medical records of patients with LFS with germline TP53 p.R337H mutation. For a better understanding of the correlation between thyroid carcinoma and LFS, tumor profile data of Brazilian carriers were analyzed. We included data from 193 patients with LFS with the TP53 p.R337H mutation from the database of the Department of Oncogenetics from the A.C. Camargo Cancer Center.
Main Outcomes and Measures Thyroid tumors found in this population were reviewed with regard to age at diagnosis, sex, histologic subtype, and other tumors presented by these patients.
Results Overall, 101 of 193 TP53 p.R337H mutation carriers with LFS from 58 families were cancer affected and, among them, thyroid carcinoma presented a prevalence of 10.9% (3 men and 8 women). The mean age at diagnosis was 44 years (median [SD], 43 [14.77] years). All the cases were histologically classified as papillary carcinomas, with 2 of them exhibiting follicular variant. The most common other cancers in the patients with thyroid carcinoma were breast cancer (5 patients) and soft-tissue sarcoma (2 patients).
Conclusions and Relevance Thyroid carcinoma may be associated with the Brazilian founder TP53 p.R337H mutation. Knowledge about this genotype/phenotype correlation is relevant to adjusting the LFS screening recommendations to these specific carriers.