RESUMO
BACKGROUND: HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. METHODS: In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression. RESULTS: We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026). CONCLUSION: Our findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1 expression might be helpful as a prognostic marker for patients with OSCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Genes Homeobox/fisiologia , Proteínas de Homeodomínio/metabolismo , Neoplasias Bucais/metabolismo , Fatores de Transcrição/metabolismo , Apoptose/fisiologia , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Adesão Celular/fisiologia , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Expressão Gênica , Proteínas de Homeodomínio/fisiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida , Fatores de Transcrição/fisiologiaRESUMO
INTRODUCTION: Gingiva fibromatosis is a relatively rare condition characterized by diffuse enlargement of the gingiva, which is caused by expansion and accumulation of the connective tissue. OBJECTIVE: The aim of the present study was to investigate proliferative and apoptotic biomarker expression in normal gingiva and two forms of gingival fibromatosis. METHODS: Archived tissue specimens of hereditary gingival fibromatosis, gingival fibromatosis and dental abnormality syndrome and normal gingiva were subject to morphological analysis and immunohistochemical staining. The results were analyzed statistically. RESULTS: Proteins associated with proliferation were found in the nuclei of epithelial cells from the basal and suprabasal layers, whereas apoptotic proteins were detected in the cytoplasm of the upper layers of the epithelium. Increased expressions of minichromosome maintenance proteins 2 and 5 were observed in the gingival fibromatosis and dental abnormality syndrome samples. In contrast, geminin expression was higher in normal gingiva samples. No difference in the expression of apoptotic proteins was observed among the groups. CONCLUSION: Our findings support a role for augmented proliferation of epithelial cells within the overgrown tissues associated with gingival fibromatosis or dental abnormality syndrome. However, our data suggest that different biological mechanisms may account for the pathogenesis of different types of gingival fibromatosis.
Assuntos
Proteínas de Ciclo Celular/análise , Células Epiteliais/química , Fibromatose Gengival/metabolismo , Proteínas Nucleares/análise , Anormalidades Dentárias/metabolismo , Biomarcadores/análise , Estudos de Casos e Controles , Estudos Transversais , Células Epiteliais/patologia , Feminino , Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Geminina , Humanos , Imuno-Histoquímica , Masculino , Componente 2 do Complexo de Manutenção de Minicromossomo , Anormalidades Dentárias/genética , Anormalidades Dentárias/patologia , Proteína X Associada a bcl-2/análiseRESUMO
INTRODUCTION: Gingiva fibromatosis is a relatively rare condition characterized by diffuse enlargement of the gingiva, which is caused by expansion and accumulation of the connective tissue. OBJECTIVE: The aim of the present study was to investigate proliferative and apoptotic biomarker expression in normal gingiva and two forms of gingival fibromatosis. METHODS: Archived tissue specimens of hereditary gingival fibromatosis, gingival fibromatosis and dental abnormality syndrome and normal gingiva were subject to morphological analysis and immunohistochemical staining. The results were analyzed statistically. RESULTS: Proteins associated with proliferation were found in the nuclei of epithelial cells from the basal and suprabasal layers, whereas apoptotic proteins were detected in the cytoplasm of the upper layers of the epithelium. Increased expressions of minichromosome maintenance proteins 2 and 5 were observed in the gingival fibromatosis and dental abnormality syndrome samples. In contrast, geminin expression was higher in normal gingiva samples. No difference in the expression of apoptotic proteins was observed among the groups. CONCLUSION: Our findings support a role for augmented proliferation of epithelial cells within the overgrown tissues associated with gingival fibromatosis or dental abnormality syndrome. However, our data suggest that different biological mechanisms may account for the pathogenesis of different types of gingival fibromatosis.
Assuntos
Feminino , Humanos , Masculino , Proteínas de Ciclo Celular/análise , Células Epiteliais/química , Fibromatose Gengival/metabolismo , Proteínas Nucleares/análise , Anormalidades Dentárias/metabolismo , Biomarcadores/análise , Estudos de Casos e Controles , Estudos Transversais , Células Epiteliais/patologia , Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Imuno-Histoquímica , Anormalidades Dentárias/genética , Anormalidades Dentárias/patologia , /análiseRESUMO
Fibromatose gengival hereditária (FGH) é uma condição genética rara, caracterizada por crescimento gengival. O objetivo deste artigo é descrever as características clínicas, histopatológicas e genéticas de duas famílias com membros afetados por FGH. Sistematicamente, todos os membros das duas famílias foram clinicamente avalidos e, quando indicado, foram cirurgicamente tratados pela combinação de gengivectomia/gengivoplastia. Embora nas duas famílias a condição tenha sido transmitida como fenótipo isolado por padrão autossômico dominante, existiu marcada diferença na penetrância e expressividade da FGH.