Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/ß-catenin pathway.

OBJECTIVE: Genomic alterations in Hürthle cell carcinomas (HCC) include chromosomal losses, mitochondrial DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/ß-catenin pathways. This study aimed at characterizing the mutational profile of HCC. METHODS: Next-generation sequencing (NGS) of 40 HCC using a 102-gene panel including, among others, the MAPK, PI3K-AKT-mTOR, Wnt/ß-catenin, and Notch pathways. HCC was widely invasive in 57.5%, and lymph node and distant metastases were diagnosed in 5% and 7.5% of cases. During follow-up, 10% of patients presented with persistent/recurrent disease, but there were no cancer-related deaths. RESULTS: Genetic alterations were identified in 47.5% of HCC and comprised 190 single-nucleotide variants and 5 insertions/deletions. The Wnt/ß-catenin pathway was most frequently affected (30%), followed by MAPK (27.5%) and PI3K-AKT-mTOR (25%). FAT1 and APC were the most frequently mutated genes and present in 17.5%. RAS mutations were present in 12.5% but no BRAF mutation was found. There was no association between the mutational profile and clinicopathological features. CONCLUSIONS: This series of HCC presents a wide range of mutations in the Wnt/ß-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/ß-catenin pathway, particularly mutations in APC and FAT1, are of particular interest. The data suggest that mutated FAT1 may represent a potential novel driver in HCC tumorigenesis and that the Wnt/ß-catenin pathway plays a critical role in this distinct thyroid malignancy.

Association between oral hygiene and head and neck cancer in Brazil.

INTRODUCTION: Poor oral hygiene, regular use of mouthwash and absence of visits to the dentist could correspond to potential risk factors for the development of head and neck cancer. OBJECTIVE: The objective of this study was to determine whether oral hygiene is associated with the occurrence of oral cavity and head and neck cancer in a Brazilian sample. METHOD: The variables of oral hygiene condition, such as toothbrushing frequency, dental loss, need and use of prosthesis, and regular visit to the dentist in a case-control study were analyzed in patients from five hospitals in the state of São Paulo, Brazil, paired by gender and age, from the multicenter project Genoma do Câncer de Cabeça e Pescoço (GENCAPO). RESULTS: The most frequent malignancies in the 899 patients included were those of the tongue border (11.41%) and tongue base (10.92%). The multivariable statistical analysis found odds ratio values: Brushing once 0.33 (95%CI 0.25 - 0.44); Brushing twice 0.42 (95%CI 0.35 - 0.52); Flossing always 0.19 (95%CI 0.13 - 0.27); Flossing sometimes 0.19 (95%CI 0.15 - 0.24); Bleeding 2.40 (95%CI 1.40 - 4.09); Prosthesis 1.99 (95%CI 1.54 - 2.56); Visiting the dentist 0.29 (95%CI 0.22 - 0.37); Good hygiene 0.21 (95%CI 0.17 - 0.27); Regular hygiene 0.20 (95%CI 0.15 - 0.25); number of missing teeth (6 or more) 3.30 (95%CI 2.67 - 4.08). CONCLUSION: These data showed that, in the population studied, indicators of good hygiene such as brushing teeth and flossing were protective factors for mouth and head and neck cancer, while bleeding and many missing teeth were risk factors.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas.

OBJECTIVE: Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. SUBJETCS AND METHODS: Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). RESULTS: Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. CONCLUSIONS: Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

Association between oral hygiene and head and neck cancer in Brazil / Associação entre higiene oral e câncer de cabeça e pescoço no Brasil

ABSTRACT: Introduction: Poor oral hygiene, regular use of mouthwash and absence of visits to the dentist could correspond to potential risk factors for the development of head and neck cancer. Objective: The objective of this study was to determine whether oral hygiene is associated with the occurrence of oral cavity and head and neck cancer in a Brazilian sample. Method: The variables of oral hygiene condition, such as toothbrushing frequency, dental loss, need and use of prosthesis, and regular visit to the dentist in a case-control study were analyzed in patients from five hospitals in the state of São Paulo, Brazil, paired by gender and age, from the multicenter project Genoma do Câncer de Cabeça e Pescoço (GENCAPO). Results: The most frequent malignancies in the 899 patients included were those of the tongue border (11.41%) and tongue base (10.92%). The multivariable statistical analysis found odds ratio values: Brushing once 0.33 (95%CI 0.25 - 0.44); Brushing twice 0.42 (95%CI 0.35 - 0.52); Flossing always 0.19 (95%CI 0.13 - 0.27); Flossing sometimes 0.19 (95%CI 0.15 - 0.24); Bleeding 2.40 (95%CI 1.40 - 4.09); Prosthesis 1.99 (95%CI 1.54 - 2.56); Visiting the dentist 0.29 (95%CI 0.22 - 0.37); Good hygiene 0.21 (95%CI 0.17 - 0.27); Regular hygiene 0.20 (95%CI 0.15 - 0.25); number of missing teeth (6 or more) 3.30 (95%CI 2.67 - 4.08). Conclusion: These data showed that, in the population studied, indicators of good hygiene such as brushing teeth and flossing were protective factors for mouth and head and neck cancer, while bleeding and many missing teeth were risk factors.

RESUMO: Introdução: Má higiene bucal, uso regular de enxaguante bucal e ausência de visitas ao dentista podem corresponder a potenciais fatores de risco para o desenvolvimento de câncer de cabeça e pescoço. Objetivo: Determinar se a higiene bucal está associada à ocorrência de câncer em cavidade oral e cabeça e pescoço em uma amostra brasileira. Método: O estudo caso controle analisou variáveis de higiene bucal, como frequência de escovação, perda dentária, necessidade e uso de prótese e visita regular ao dentista em pacientes de cinco hospitais do estado de São Paulo, pareados por sexo e idade, provenientes do projeto multicêntrico Genoma do Câncer de Cabeça e Pescoço (GENCAPO). Resultados: As neoplasias mais frequentes nos 899 pacientes incluídos foram: bordo de língua (11,41%) e base de língua (10,92%). A análise estatística múltipla encontrou os seguintes valores de odds ratio: escovar uma vez 0,33 (IC95% 0,25 - 0,44); escovar duas vezes 0,42 (IC95% 0,35 - 0,52); uso de fio dental sempre 0,19 (IC95% 0,13 - 0,27); uso de fio dental às vezes 0,19 (IC95% 0,15 - 0,24); sangramento 2,40 (IC95% 1,40 - 4,09); prótese 1,99 (IC95% 1,54 - 2,56), visita ao dentista 0,29 (IC95% 0,22 - 0,37); boa higiene 0,21 (IC95% 0,17 - 0,27); higiene regular 0,20 (IC95% 0,15 - 0,25); e número de dentes ausentes (6 ou mais) 3,30 (IC95% 2,67 - 4,08). Conclusões: Esses dados mostraram que, na população estudada, indicadores de boa higiene, como escovar os dentes e uso do fio dental, foram fatores de proteção para o câncer de boca e cabeça e pescoço, enquanto sangramento e muitos dentes ausentes foram fatores de risco.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas

ABSTRACT Objective Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. Subjetcs and methods Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). Results Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. Conclusions Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

Análise crítica do tratamento atual para o carcinoma espinocelular precoce de língua oral e soalho com invasão perineural / Critical assessment of the current treatment for initial squamous cell carcinoma of tongue and floor of mouth with perineural invasion

Introdução: O espaço perineural é reconhecido como rota de propagação do carcinoma espinocelular (CEC) e, quando acometido, tem sido relacionado com pior prognóstico, maior recorrência e menor tempo de sobrevivência. Contudo, seu papel nos tumores precoces de cavidade oral ainda não está totalmente esclarecido. Objetivos: comparar a sobrevivência global e livre de doença entre pacientes com carcinoma espinocelular precoce de língua oral e soalho de boca com e sem invasão perineural; comparar a ocorrência de fatores clínicos e anátomo-patológicos entre os grupos; e descrever os casos de óbito para análise crítica da realização do tratamento radioterápico adjuvante. Métodos: Foi realizado estudo retrospectivo longitudinal de caso-controle, de 42 pacientes operados por CEC precoce (T1/T2 N0) de língua oral e soalho de boca, divididos em dois grupos: com invasão perineural (n=16) e sem invasão (n=26). Variáveis clínicas, anátomo-patológicas e de seguimento, incluindo realização de tratamento adjuvante foram comparadas. Resultados: No grupo com invasão perineural houve maior freqüência de homens (p=0,008), óbito relacionado (p=0,015), quantidade de cigarro consumida (p=0,042) e menor freqüência de não etilistas. As médias do maior diâmetro (p=0,046) e da espessura (p=0,002) do CEC primário foram maiores nesse grupo. Conclusões: Houve menor sobrevivência global no grupo de doentes com CEC precoce de língua oral e soalho com invasão perineural (p=0,019), apesar da maior freqüência de radioterapia adjuvante. Todos os óbitos relacionados ocorreram no grupo com invasão perineural, por recidiva local, sendo que, em dois casos, nenhuma outra característica de mau prognóstico foi observada. À análise multivariada, a presença de invasão perineural foi indicada como fator associado ao óbito correlacionado, de maneira não significante (p=0,275). Os resultados favorecem a indicação de tratamento radioterápico adjuvante.

Introduction: perineural space is known as a pathway for spreading of the squamous cell carcinoma (SCC). Its invasion has been associated with worse prognosis, greater rates of recurrence and lower survival rates. However, its impact on the initial oral cavity tumors is not well established. Objectives: to compare global survival and disease free survival between patients with initial SCC of tongue and floor of mouth, with and without perineural invasion; to compare clinical and pathological features between the two groups; and to describe the cases of death for a critical analysis of the use of adjuvant radiotherapy. Methods: retrospective longitudinal case-control study of 42 patients surgically treated for initial SCC (T1/T2 N0 ? UICC-2002) of oral tongue and floor of mouth. The patients were divided into two groups: with (n=16) and without (n=26) perineural invasion. Clinical and pathological features, as well as the follow-up and treatment information were compared. Results: the group with perineural invasion presented a higher frequency of male patients (p=0.008) and of tobacco use (p=0.042) and lower frequency of non users of alcohol. The mean of greater tumor diameter (p=0.046) and thickness (p=0,002) were higher in this group. Those patients also had higher disease specific death (p=0.015) and a lower survival (p=0.019), regardless of a higher frequency of adjuvant treatment with radiotherapy. All disease specific deaths occurred in this group and, in two of these cases, no other known features of worse prognosis were observed. At the multivariate analysis, the perineural invasion was related to disease-specific death in a non significant manner (p=0.275). Conclusion: These results point out the perineural invasion as a feature of worse prognosis, even in initial tumors and despite more aggressive treatment.