AGK-BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma.

BACKGROUND: The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen-activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation-exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. PROCEDURE: In this study, we investigated the prevalence of BRAF alterations (AGK-BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK-BRAF fusion was investigated by RT-PCR and confirmed by FISH break-apart. The BRAF V600E mutation was screened using Sanger sequencing. RESULTS: AGK-BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. CONCLUSION: Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.

Thyroid-Specific Genes Expression Uncovered Age-Related Differences in Pediatric Thyroid Carcinomas.

Despite a more advanced stage of disease at presentation, a better response to radioiodine (RAI) therapy and a reduced overall mortality have been reported in pediatric differentiated thyroid cancer (DTC) in comparison to adult DTC. Few studies suggested that the better response to RAI therapy in pediatric patients might be associated with an increased expression of NIS. However, a marked heterogeneity within the pediatric group has been recognized. Children (<10 years old) usually present a more aggressive disease than adolescents (≥10-18 years old). By analyzing the expression of thyroid-specific genes in 38 sporadic pediatric tumors, we show that the expression of NIS, PDS, and TSHR was lower in children than adolescents (P < 0.05). A linear regression confirmed the association between NIS expression and age. Most significantly, NIS was expressed at similar levels in DTC from children and adults, whereas PDS and TSHR expression was even lower in DTC from children, compared to adolescents and adults. Our data suggest that biological behaviors of DTC in adolescents might differ from those in children and adults. Therefore, the premise that the expression of thyroid-specific genes is higher in tumors from pediatric patients than in adults is not entirely true and might be too oversimplified.

Study of the histological profile of papillary thyroid carcinomas associated with Hashimoto's thyroiditis.

OBJECTIVE: To investigate the association between the histological parameters of papillary thyroid cancer (PTC) and the presence of Hashimoto's thyroiditis (HT). MATERIALS AND METHODS: Histological samples from patients with PTC were reviewed by an endocrine pathologist. The following parameters were analyzed: presence of concomitant HT, multifocality, presence of nodal metastasis, tumor size, vascular invasion, perineural infiltration, histological variant, and pathological staging. Clinical data included gender and age at the time of the diagnosis. RESULTS: A total of 94 cases of PTC were reviewed. There was a predominance of women (85.1% vs. 14.9%) and median age at presentation was 45.13 years. The presence of HT was significantly associated with greater occurrence of multifocal tumors (p = 0.004), early pathological stage (p = 0.02), and smaller tumor size (p = 0.025). CONCLUSIONS: Patients with PTC associated with HT had significantly smaller tumors, more often multifocal and in an earlier stage than their counterparts without HT. A better understanding of the immune response involved in these tumors may be useful for future strategies on the prevention and for the development of new therapeutic approaches for this group of neoplasms.

Study of the histological profile of papillary thyroid carcinomas associated with Hashimoto's thyroiditis / Estudo do perfil histológico de carcinomas papilíferos de tireoide associados à tireoidite de Hashimoto

OBJECTIVE: To investigate the association between the histological parameters of papillary thyroid cancer (PTC) and the presence of Hashimoto's thyroiditis (HT). MATERIALS AND METHODS: Histological samples from patients with PTC were reviewed by an endocrine pathologist. The following parameters were analyzed: presence of concomitant HT, multifocality, presence of nodal metastasis, tumor size, vascular invasion, perineural infiltration, histological variant, and pathological staging. Clinical data included gender and age at the time of the diagnosis. RESULTS: A total of 94 cases of PTC were reviewed. There was a predominance of women (85.1% vs. 14.9%) and median age at presentation was 45.13 years. The presence of HT was significantly associated with greater occurrence of multifocal tumors (p = 0.004), early pathological stage (p = 0.02), and smaller tumor size (p = 0.025). CONCLUSIONS: Patients with PTC associated with HT had significantly smaller tumors, more often multifocal and in an earlier stage than their counterparts without HT. A better understanding of the immune response involved in these tumors may be useful for future strategies on the prevention and for the development of new therapeutic approaches for this group of neoplasms.

OBJETIVO: Investigar a associação entre parâmetros histológicos do carcinoma papilífero da tireoide (CPT) e a presença de tireoidite de Hashimoto (TH). MATERIAIS E MÉTODOS: Amostra de tecidos de CPT foi revista por um médico patologista. Os seguintes parâmetros foram avaliados: presença de TH concomitante, multicentricidade, metástase linfonodal, tamanho tumoral, invasão vascular, infiltração perineural, variante histológica e estadiamento patológico. Os dados clínicos incluíam gênero e idade ao diagnóstico. RESULTADOS: Um total de 94 casos de CPT foi revisto. Houve predomínio do sexo feminino (85,1% vs. 14,9%) e a idade média de apresentação foi de 45,13 anos. A presença de TH foi associada a maior ocorrência de tumores multifocais (p = 0,004), estágios iniciais de estadiamento (p = 0,02) e tumores menores (p = 0,025). CONCLUSÃO: O CPT associado a TH apresentou-se com menor dimensão, maior ocorrência de multifocalidade e em estadiamentos mais iniciais do que os casos de CPT sem TH associada. Um melhor entendimento da resposta imune envolvida nesses tumores pode ser útil para estratégias futuras de prevenção e para o desenvolvimento de novas abordagens terapêuticas para esse tipo de neoplasia.