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OBJECTIVES: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. METHODS: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. RESULTS: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. CONCLUSION: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.
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Apoptose , Artemisininas , Movimento Celular , Cisplatino , Progressão da Doença , Leucoplasia Oral , Neoplasias Bucais , Artemisininas/farmacologia , Animais , Leucoplasia Oral/patologia , Leucoplasia Oral/tratamento farmacológico , Humanos , Cisplatino/farmacologia , Camundongos , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proteína HMGB1/metabolismo , Antineoplásicos/farmacologiaRESUMO
Oral squamous cell carcinoma (OSCC) has a poor prognosis and the treatment employed generates significant physical deformity in patients. In recent years, an increase in the incidence of cases of OSCC has been observed in adult patients up to 45 years old in several genetic underrepresented and underserved countries. The increase in OSCC cases in young people is very relevant because it shows that OSCC does not make exceptions and hereditarily must play an important role. This fact has not been associated with an evident biological basis, and a large majority of these patients do not present the classic principal risk factors association. OSCC is the result of accumulation of genetic and epigenetic alterations and this information is still fragmented in the literature, mainly in the young group. Conducting studies with a comprehensive analysis of genetic and epigenetic data is crucial, to provide greater understanding of the underlying biology of OSCC, because this information can be decisive to determine targets for therapeutic treatment. We review the main germline and somatic aspects of genetic and genomic variation in OSCC considering the absence of genomic data from developing countries such as Chile and the rest of Hispano-America.
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Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.
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El granuloma piogénico es una lesión vascular reactiva benigna del tejido blando que surge en respuesta a irritantes crónicos de bajo grado. Rara vez crece más de 2 cm de diámetro y por lo general, no provoca cambios en el hueso alveolar. Presentamos un caso inusual de granuloma piógeno en una mujer de 19 años, de extenso tamaño y comportamiento agresivo, asociado a resorción ósea severa, movilidad dentaria, hemorragia, anemia ferropénica y recurrencias.
Pyogenic granuloma is a benign reactive vascular lesion of the soft tissue that arises in response to chronic low-grade irritants. It rarely grows more than 2 cm in diameter and usually does not cause changes in the alveolar bone. We present the case of a 19-year-old woman with an unusual pyogenic granuloma of extensive size and aggressive behavior, associated with severe bone resorption, tooth mobility, hemorrhage, iron deficiency anemia and recurrences.
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Humanos , Feminino , Adulto , Reabsorção Óssea , Granuloma PiogênicoRESUMO
The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Sequenciamento do Exoma , Neoplasias de Cabeça e Pescoço/patologia , Mucosa Bucal/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologiaRESUMO
Abstract The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.
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This report presents the clinical, microscopic and immunohistochemical aspects of a case of proliferative verrucous leukoplakia (PVL) mimicking oral lichen planus (OLP) in a 66-year-old woman. We also review the literature reporting cases of PVL mimicking OLP, where we found a higher prevalence in women who do not consume tobacco or alcohol. The initial manifestation of lichenoid areas was around the age of 59, with the diagnosis of PVL being established on average 6 years later, while malignant transformation occurred in 8 of the 22 cases at an average of 3.7 years after the final diagnosis of PVL. We emphasize the need for a close follow-up of any patient presenting white lesions of the oral mucosa. Lesions that are clinically and microscopically compatible with lichenoid reactions or OLP must be investigated and differentiated from PVL, which has a worse prognosis.
Este relato apresenta os aspectos clínicos, microscópicos e imuno-histoquímicos de um caso de leucoplasia verrucosa proliferativa (LPV) mimetizando líquen plano oral (LPO) em uma paciente do sexo feminino de 66 anos. Também revisamos a literatura relatando casos de LPV mimetizando LPO, onde encontramos maior prevalência em mulheres que não consomem tabaco ou álcool, com manifestação inicial de áreas liquenoides por volta dos 59 anos, sendo estabelecido o diagnóstico de LPV em média 6 anos depois, enquanto a transformação maligna ocorreu em 8 dos 22 casos em média 3,7 anos após o diagnóstico final de LPV. Ressaltamos a necessidade de acompanhamento rigoroso de qualquer paciente que apresente lesões brancas da mucosa oral, devendo ser investigadas lesões clinicamente e microscopicamente compatíveis com reações liquenóides ou LPO e diferenciadas da LPV, que tem pior prognóstico
Este reporte presenta los aspectos clínicos, microscópicos e inmunohistoquímicos de un caso de leucoplasia verrugosa proliferativa (LVP) simulando liquen plano oral (LPO) en una paciente de 66 años. También revisamos la literatura reportando casos de LVP simulando LPO, donde encontramos una mayor prevalencia en mujeres que no consumen tabaco ni alcohol, con una manifestación inicial de áreas liquenoides alrededor de los 59 años, estableciéndose el diagnóstico de LVP en promedio 6 años después, mientras que la transformación maligna ocurrió en 8 de los 22 casos en un promedio de 3,7 años después del diagnóstico final de LVP. Resaltamos la necesidad de un seguimiento estrecho de todo paciente que presente lesiones blanquecinas de la mucosa oral, que las lesiones clínica y microscópicamente compatibles con reacciones liquenoides o LPO deben ser investigadas y diferenciadas de la LVP, que tienen peor pronóstico.
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Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. OBJECTIVE: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. MATERIAL AND METHODS: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. RESULTS: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. CONCLUSION: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.
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Amelogênese Imperfeita/diagnóstico por imagem , Amelogênese Imperfeita/genética , Genealogia e Heráldica , Padrões de Herança , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amelogênese Imperfeita/epidemiologia , Amelogênese Imperfeita/patologia , Criança , Pré-Escolar , Chile/epidemiologia , Esmalte Dentário/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Distribuição por Sexo , Estatísticas não Paramétricas , Adulto JovemRESUMO
Abstract Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. Objective: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. Material and Methods: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. Results: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. Conclusion: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.
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Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Padrões de Herança , Amelogênese Imperfeita/genética , Amelogênese Imperfeita/diagnóstico por imagem , Genealogia e Heráldica , Fenótipo , Chile/epidemiologia , Distribuição por Sexo , Estatísticas não Paramétricas , Esmalte Dentário/patologia , Amelogênese Imperfeita/patologia , Amelogênese Imperfeita/epidemiologia , Pessoa de Meia-IdadeRESUMO
RESUMEN: El carcinoma oral de células escamosas es la neoplasia maligna más frecuente en la cavidad oral. Sin embargo, los estudios sobre supervivencia general en pacientes con cáncer oral son escasos en Chile. Objetivo: Determinar las características sociodemográficas y la supervivencia general de pacientes diagnosticados con carcinoma en labio y cavidad oral en el Servicio de Anatomía Patológica de la Facultad de Odontología, Universidad de Chile. Material y métodos: Se seleccionaron los casos de carcinoma oral de células escamosas diagnosticados entre los años 2000-2012. Se incluyeron sólo los primeros diagnósticos y las recidivas fueron excluidas. Resultados: De 134 casos registrados, 120 cumplían los criterios de inclusión. El 60% correspondió a hombres (razón hombre-mujer 1,3:1) y la media de edad fue 63 años. La supervivencia general a dos años fue 48,3% y a cinco años 33,9% según estimación de Kaplan-Meier. Se detectó una mayor supervivencia en el grupo de pacientes que tenían menos de 55 años (p<0,05). 79,2% de los casos fallecidos registra como causa de muerte cáncer oral. Conclusiones: El mayor porcentaje de personas diagnosticadas fueron hombres y adultos mayores. La supervivencia general a cinco años fue menor a lo determinado en reportes nacionales previos. Los adultos de 55 años y mayores presentaron una menor supervivencia general.
ABSTRACT: Oral squamous cell carcinoma is the most common malignant neoplasm of oral cavity. Research about general survival rates in patients with oral cancer is limited in Chile. Objective: To determine the sociodemographic characteristics and general survival of patients diagnosed with lip and oral carcinoma in the Pathological Anatomy Service at the School of Dentistry, University of Chile. Material and methods: All cases of oral squamous cell carcinoma selected were diagnosed between the years 2000 and 2012. All cases included in this study corresponded to the first diagnosis and tumor recurrence was excluded. Results: The 134 registered cases, 120 were selected with inclusion criteria. 60% were men (male and female ratio of 1.3: 1) and median age 63 year-old. Overall survival at two years was 48.3% and at five years 33.9%, according to Kaplan-Meier estimate. A higher survival was detected in the group of patients younger than 55 years old (p <0.05). In 79.2% of dead patients, the cause of death was registered as oral cancer. Conclusions: The highest percentage of patients diagnosed was men and elders. Five-year survival was lower than previously reported in national reports. Adults aged 55 years and older had a lower overall survival.