Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma

Maria Rosa Bella-Cueto, Antónia Afonso Póvoa, Elisabete Teixeira, Rui Batista, Ana Pestana, Miguel Melo, Thalita Alves, Mafalda Pinto, Manuel Sobrinho-Simões, Jorge Maciel, Paula Soares

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Resum

Aggressive metastatic disease is rare in papillary thyroid carcinoma (PTC), a neoplasia that usually carries an excellent prognosis. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We performed Sanger sequencing on a series of 241 PTCs to determine the role of genetic mutations (BRAF, RAS, and TERTp) in PTC patient outcomes. The implication of RAS mut tumors remain uncertain in clinical terms. BRAF mut /TERTp wt tumors were prone to be associated with local aggressiveness (recurrent, persistent/disease), whereas TERTp mut tumors were predisposed to recurrent/persistent structural disease, and disease-specific mortality. Our results indicate that different molecular markers play a distinct role in predicting PTC patient outcomes. Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002-2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTp mut showed increased risk of structural disease (HR = 7.0, p < 0.001) and DSM (HR = 10.1, p = 0.001). Combined genotypes, BRAF wt /TERTp mut (HR = 6.8, p = 0.003), BRAF mut /TERTp mut (HR = 3.2, p = 0.056) and BRAF mut /TERTp wt (HR = 2.2, p = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAF wt /TERTp mut (HR = 24.2, p < 0.001) and BRAF mut /TERTp mut (HR = 11.5, p = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTp mut regardless of BRAF status (BRAF mut /TERTp mut, log-rank p < 0.001; BRAF wt /TERTp mut, log-rank p < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients' outcome. BRAF mut /TERTp wt tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTp mut tumors were predisposed to recurrent structural disease and DSM.
Idioma originalEnglish
RevistaCancers
Volum13
DOIs
Estat de la publicacióPublicada - 2021

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