RESUMO
BACKGROUND: Currently, treatment recommendations for papillary thyroid carcinoma are not based on the genetic background causing tumourigenesis. The aim of the present study was to correlate the mutational profile of papillary thyroid carcinoma with clinical parameters of tumour aggressiveness, to establish recommendations for risk-stratified surgical treatment. METHOD: Papillary thyroid carcinoma tumour tissue of patients undergoing thyroid surgery at the University Medical Centre Mainz underwent analysis of BRAF, TERT promoter and RAS mutational status as well as potential RET and NTRK rearrangements. Mutation status was correlated with clinical course of disease. RESULTS: One hundred and seventy-one patients operated for papillary thyroid carcinoma were included. The median age was 48 years (range 8-85) and 69 per cent (118/171) of patients were females. One hundred and nine papillary thyroid carcinomas were BRAF-V600E mutant, 16 TERT promotor mutant and 12 RAS mutant; 12 papillary thyroid carcinomas harboured RET rearrangements and two papillary thyroid carcinomas showed NTRK rearrangements. TERT promoter mutant papillary thyroid carcinomas had a higher risk of distant metastasis (OR 51.3, 7.0 to 1048.2, P < 0.001) and radioiodine-refractory disease (OR 37.8, 9.9 to 169.5, P < 0.001). Concomitant BRAF and TERT promoter mutations increased the risk of radioiodine-refractory disease in papillary thyroid carcinoma (OR 21.7, 5.6 to 88.9, P < 0.001). RET rearrangements were associated with a higher count of tumour-affected lymph nodes (OR 7950.9, 233.7 to 270495.7, P < 0.001) but did not influence distant metastasis or radioiodine-refractory disease. CONCLUSIONS: Papillary thyroid carcinoma with concomitant BRAF-V600E and TERT promoter mutations demonstrated an aggressive course of disease, suggesting the need for a more extensive surgical strategy. RET rearrangement-positive papillary thyroid carcinoma did not affect the clinical outcome, potentially obviating the need for prophylactic lymphadenectomy.
Assuntos
Carcinoma Papilar , Carcinoma , Telomerase , Neoplasias da Glândula Tireoide , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Carcinoma/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/cirurgia , Proteínas Proto-Oncogênicas B-raf/genética , Radioisótopos do Iodo , Telomerase/genética , Medição de RiscoRESUMO
The need for integration of vertical projects into the Basic Health Services (BHS) has been felt in Nepal since 1968. In 1987 it was decided to provide integrated BHS all over the country. The Nepal Leprosy Control Project (NLCP) was one of the vertical projects which had to be integrated from that year. In order to prepare the BHS staff for this new task the NLCP developed a Comprehensive Leprosy Training course. Besides adequate training, three other prerequisites for successful integration are: a) adequate supply of drugs and equipment; b) regular supervision and specialist referral facilities; and c) a well functioning BHS system in which to integrate. This article tries to assess to what extent these prerequisites have been met for leprosy control in Nepal. To do this, some results of an evaluation of the training are used as well as existing literature on the functioning of the BHS system. The first three prerequisites are not fully met, but problems and obstacles related to these are mainly due to problems in the last prerequisite: a not so well functioning BHS system. It was, therefore, recommended to continue a (semi)vertical support system of leprosy control in those districts where the BHS is not so well developed