RESUMO
The human patched gene (PTCH) functions in both embryologic development and tumor suppression. PTCH mutations have been found in odontogenic keratocysts. However, the expression and localization of the protein product of the gene have not been determined in odontogenic tumors and cysts. We investigated 68 odontogenic lesions by immunohistochemistry, and compared their PTCH expression with that in basal cell carcinomas. All odontogenic lesions, including two keratocysts with truncating mutations, were positive for PTCH. Different types of lesions had different amounts of staining. Lack of staining was noted in the majority of basal cell carcinomas. Taken together, these data suggest that odontogenic keratocysts arise with heterozygous mutations of the PTCH gene.
Assuntos
Proteínas de Membrana/análise , Proteínas de Neoplasias/análise , Cistos Odontogênicos/genética , Tumores Odontogênicos/genética , Sequência de Aminoácidos , Carcinoma Basocelular/química , Carcinoma Basocelular/genética , Genes Supressores de Tumor , Heterozigoto , Humanos , Técnicas Imunoenzimáticas , Proteínas de Membrana/genética , Dados de Sequência Molecular , Mutação , Proteínas de Neoplasias/genética , Cistos Odontogênicos/química , Tumores Odontogênicos/química , Receptores Patched , Receptor Patched-1 , Receptores de Superfície CelularRESUMO
An odontogenic keratocyst (OKC) is a benign cystic lesion of the jaws that occurs sporadically or in association with nevoid basal cell carcinoma syndrome (NBCCS). Recently, the gene for NBCCS was cloned and shown to be the human homologue of the Drosophila segment polarity gene Patched (PTCH), a tumor suppressor gene. The PTCH gene encodes a transmembrane protein that acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues, including tooth. We investigated three cases of sporadic odontogenic keratocysts and three other cases associated with NBCCS, looking for mutations of the PTCH gene. Non-radioactive single-strand conformational polymorphism and direct sequencing of PCR products revealed a deletion of 5 base pairs (bp) in exon 3 (518delAAGCG) in one sporadic cyst as well as mutations in two cysts associated with NBCCS, a nonsense (C2760A) and a missense (G3499A) alteration. This report is the first to describe a somatic mutation of PTCH in sporadic odontogenic keratocysts as well as two novel mutations in cysts associated with NBCCS, indicating a similar pathogenesis in a subset of sporadic keratocysts.
Assuntos
Proteínas de Membrana/genética , Mutação/genética , Cistos Odontogênicos/genética , Transativadores , Adulto , Substituição de Aminoácidos/genética , Síndrome do Nevo Basocelular/genética , Pareamento de Bases/genética , Códon sem Sentido/genética , Indução Embrionária/genética , Éxons/genética , Feminino , Mutação da Fase de Leitura/genética , Deleção de Genes , Genes Supressores de Tumor/genética , Proteínas Hedgehog , Humanos , Masculino , Mutação de Sentido Incorreto/genética , Receptores Patched , Receptor Patched-1 , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Proteínas/genética , Receptores de Superfície Celular , Análise de Sequência de DNA , Transdução de Sinais/genéticaRESUMO
We describe an 8-year-old boy who presented with severe facial swelling. This progressed rapidly and 17 months later he died of gastrointestinal and pulmonary infections. The diagnosis was initially brown tumour associated with hyperparathyroidism, but this was revised in the light of laboratory investigations that were within the reference ranges, and normal appearance of the parathyroids on exploration to that of an extreme case of cherubism that behaved in a locally aggressive manner.
Assuntos
Querubismo/patologia , Criança , Diagnóstico Diferencial , Evolução Fatal , Humanos , Hiperparatireoidismo Secundário/diagnóstico , Neoplasias Maxilomandibulares/diagnóstico , MasculinoRESUMO
The odontogenic keratocyst (OKC) is a clinic and histologically distinct form of odontogenic cyst. It is known for its aggressive behaviour, high recurrence rate and may be in association with nevoid basal cell carcinoma syndrome. Recently was reported that the lost of human patched (ptch), a tumour suppressor gene, is the possible molecular origin of the OKC. This report reviews the clinic, histologic and molecular characteristics of OKCs. Treatment and recurrence are discussed too.
Assuntos
Cistos Odontogênicos/diagnóstico , Humanos , Cistos Odontogênicos/genética , Cistos Odontogênicos/terapiaRESUMO
Glandular odontogenic cyst (GOC) is a rare jawbone cyst of odontogenic origin. Human patched (PTCH) is a tumour suppressor gene that has been recently associated with signalling pathways during odontogenesis. Recently alterations of this gene were found on sporadic odontogenic keratocysts. This evidence, together with the biological behaviour similarities of both lesions, and the absence of reports on molecular analysis of GOC, led us to hypothesize that PTCH gene mutations may underlie the tumorigenesis of GOC. Therefore the aim of this study was to report one additional case of GOC and investigate the PTCH gene of the cyst. No mutations were found in the splicing and coding regions of the PTCH gene. In conclusion, the PTCH gene does not seem to be involved in GOC pathogenesis.
Assuntos
Doenças Mandibulares/genética , Proteínas de Membrana/genética , Mutação/genética , Cistos Odontogênicos/genética , Idoso , Éxons/genética , Feminino , Amplificação de Genes , Humanos , Doenças Mandibulares/patologia , Odontogênese/genética , Cistos Odontogênicos/patologia , Receptores Patched , Receptor Patched-1 , Receptores de Superfície Celular , Análise de Sequência de DNA , Transdução de Sinais/genéticaRESUMO
The immunohistochemical expression of PCNA and Ki-67 proteins and the histochemical expression of AgNORs were studied in 20 odontogenic keratocysts in order to assess the relationship between epithelial cell proliferation and inflammation within the capsule. Immunostained cells were quantified by conventional methods, and both quantitative and morphometric analyses of AgNORs were performed by TV image analysis. Non-inflamed odontogenic keratocysts showed a typical epithelial lining and inflamed odontogenic keratocysts were lined also by hyperplastic non-keratinized stratified squamous epithelium. A statistically significant increase of PCNA+ and Ki-67+ cells and of AgNOR numbers was detected in the linings of inflamed odontogenic keratocysts compared to non-inflamed lesions. The results suggest the existence of greater proliferative activity in the epithelial cells of inflamed odontogenic keratocysts, which may be associated with the disruption of the typical structure of odontogenic keratocyst linings.
Assuntos
Inflamação/patologia , Cistos Odontogênicos/patologia , Biomarcadores , Divisão Celular , Células Epiteliais/patologia , Humanos , Técnicas Imunoenzimáticas , Queratinas , Antígeno Ki-67/análise , Região Organizadora do Nucléolo/patologia , Antígeno Nuclear de Célula em Proliferação/análise , Coloração pela PrataRESUMO
Cysticercosis is a condition in which a human acts as the intermediate host of the pork tapeworm Taenia solium. Although cysticercosis is a common disease in some regions of the world and can occur in any body site, oral lesions are rare. This paper reviews the natural history of the disease and reports on seven cases of oral cysticercosis.