Epithelial-mesenchymal transition related to bone invasion in oral squamous cell carcinoma.

INTRODUCTION: Bone invasion is an important prognostic factor in oral squamous cell carcinoma, leading to a lower survival rate and the use of aggressive treatment approaches. Epithelial-mesenchymal transition (EMT) is possibly involved in this process, because it is often related to mechanisms of cell motility and invasiveness. This study examined whether a panel of epithelial-mesenchymal markers are present in cases of oral squamous cell carcinoma with bone invasion and whether these proteins have any relationship with patients' clinical-pathological parameters and prognostic factors. METHODS: Immunohistochemical analysis of E-cadherin, twist, vimentin, TGFß1, and periostin was performed in paraffin-embedded samples of 62 oral squamous cell carcinoma cases. RESULTS: The analysis revealed that most cases (66%) presented with a dominant tumor infiltrative pattern in bone tissue, associated with lower survival rates, when compared with cases with a dominant erosive invasion pattern (P = 0.048). Twenty-seven cases (43%) expressed markers that were compatible with total or partial EMT at the tumor-bone interface. There was no association between evidence of total or partial EMT and other demographic or prognostic features. E-cadherin-positive cases were associated with tobacco smoking (P = 0.022); vimentin-positive cases correlated with tumors under 4 cm (P = 0.043). Twistexpression was observed in tumors with a dominant infiltrative pattern (P = 0.041) and was associated with the absence of periostin (P = 0.031). CONCLUSION: We observed evidence of total or partial EMT in oral squamous cell carcinoma bone invasion. The transcription factor twist appears to be involved in bone invasion and disease progression.

Oral Squamous Cell Carcinoma Bone Invasion: Possible Roles of E-Cadherin in Osteoclastogenesis and Bone Infiltration.

INTRODUCTION: Squamous cell carcinoma is the most common cancer of the oral cavity. When the tumor invades the bone tissue, the prognostic and survival rates decrease a lot, and the treatment becomes more aggressive, with several damages to the patient and health system. Many of the molecular mechanisms of bone invasion process are not understood yet, but it is already known that one of central processes of tumor evolution - adjacent tissues invasion and metastasis - is a large spectrum of phenotypic changes in epithelial cells to mesenchymal, in a process named as epithelial-mesenchymal transition (EMT). Loss of E-cadherin, an important epithelial cell adhesion protein, is a hallmark of this phenomenon. The objective of this retrospective study is to evaluate the expression of E-cadherin protein, comparing its distribution with clinical characteristics of the patients and possibly relation to EMT. METHODS: Sixty-two cases with respective clinical data were analyzed by comparing immunohistochemical, H and E staining, and clinical data, observing the tumor-bone interface (TBI) and the surrounding tumor that had no direct contact with the bone surface (ST). RESULTS: Forty cases were positive for E-cadherin (64%) with a heterogeneous pattern. Statistical analysis showed a significant difference between the presence of E-cadherin expression and tobacco smokers. Also, the equal or weaker protein expression in the ST than TBI is related to a worse overall survival. No statistically significant difference in other prognostic factors was observed. CONCLUSION: Our results suggest that the tumor cells that interact with the bone tissue could gain molecular changes, like partial EMT and osteoclastogenesis induction, which facilitate their migration and increase the bone resorption, resulting in a worse patient's prognosis.

Claudin expression is maintained in mucoepidermoid carcinoma of the salivary gland.

OBJECTIVE: The aim of the present study was to investigate the expression of claudin-1, -3, -4, -5 and -7 proteins in mucoepidermoid carcinoma of oral cavity and analyze whether EGF may interfere in the expression of the genes that encode claudins using in vitro models. MATERIAL AND METHODS: Using immunohistochemistry, the expression of claudins was searched in 36 histologically graded cases of mucoepidermoid carcinoma. The association of expression of claudins with clinical-pathological parameters was evaluated. An in vitro step investigated the influence of EGF on gene expression of claudins by real time RT-PCR technique. RESULTS: Claudin-1, -3, -4, -5, and -7 were highly expressed in most mucoepidermoid carcinomas. These expressions were compared with clinicopathological parameters. High expression of claudin-1 was associated with patients over 40 years-old (p = 0.05) and Caucasians (p = 0.024). In vitro experiments demonstrated a tendency for Claudin gene expression increase after EGF stimulus. CONCLUSIONS: The expression of claudins is maintained in mucoepidermoid carcinoma cells and EGF could be related with this expression. Our results point out to a fundamental biological importance to CLDNs in normal and neoplastic tissue. The expression patterns of CLDNs does not yet allow a clinical application, but the biological knowledge will ground evidence to new studies towards possible target-therapies.

Simple Bone Cyst Mimicking Stafne Bone Defect.

Stafne bone defects (SBDs) are asymptomatic lingual bony defects in mandible, which are usually detected as an incidental finding in plain radiographs. Similarly, simple bone cysts (SBCs) are most frequently found in posterior region of the mandible and also are asymptomatic. However, due to anatomical structures overlap in plain radiographs, there is a possibility of misdiagnosing SBD that often is diagnosed by presumptive diagnosis observed in plain radiograph. This report shows an unusual case that a SBC resembles a SBD.

Osteoporose induzida por glicocorticoides: expressão salivar de biomarcadores ósseos em pacientes submetidos à corticoterapia prolongada e sua correlação radiomorfométrica / Glucocorticoid-induced osteoporosis: salivary expression of bone turnover biomarkers and radiomorphometric analysis in long-term corticotherapy

A osteoporose, alteração osteometabólica crônico-degenerativa, de etiologia multifatorial, caracteriza-se pela redução da densidade mineral óssea, na qual observa-se a deterioração da microarquitetura óssea, com consequentes alterações nas propriedades físicas e quantitativas do esqueleto humano, tornando-o frágil e suscetível ao desenvolvimento de fraturas. A doença é classificada em primária e secundária, de acordo com sua etiopatogênese, sendo a osteoporose induzida por glicocorticoides (OPIG) a mais incidente dentre as tipologias secundárias. Evidencia-se alterações microarquiteturais ósseas, resultantes do regime crônico de altas doses medicamentosas, sendo seu diagnóstico realizado a partir da análise quantitativa da massa óssea pelo exame padrão densitometria óssea por absorciometria por dupla emissão de raios X. Não obstante, ainda se perpetua como um grande desafio às equipes multidisciplinares de saúde, caracterizando-se como uma técnica de alto custo e de acesso limitado a maior parte da população. Com o intuito de implementar abordagens menos invasivas e mais acessíveis no rastreio de osteoporose induzida por glicocorticoides, o presente estudo propôs analisar o impacto da corticoterapia prolongada pela avaliação bioquímica salivar comparativa de biomarcadores ósseos, associada ao estudo radiomorfométrico de radiografias panorâmicas de mandíbula, pelo índice mandibular cortical (IMCo), em dois tempos distintos. Nossa investigação observou reduções estatisticamente relevantes, em relação aos dados densitométricos de pacientes submetidos à corticoterapia prolongada, os quais, um ano após a instituição medicamentosa (T1), resultaram em valores de T-score de coluna e femoral significativamente alterados (p<0,0001 e p=0,0122, respectivamente), sendo que mais da metade (56%) dos pacientes apresentou redução da densidade mineral óssea, quando comparado ao início da corticoterapia (p=0,0002). O impacto do regime terapêutico prolongado refletiu significativamente no índice de massa corpórea dos doentes (p=0,0156). A partir da aferição do índice mandibular cortical em radiografias panorâmicas dos participantes, pôde-se observar diferença estatisticamente significante (p<0,0001), entre os dois tempos avaliados, e uma forte correlação entre si (rs=0,7952); tal como correlação positiva entre o índice mandibular e a classificação densitométrica instituída pela Organização Mundial da Saúde (T0, p=0,0443 e, em T1, p=0,3266). Adicionalmente, por meio do imunoensaio Luminex®, avaliamos a expressão salivar dos biomarcadores relacionados ao turnover ósseo Osteoprotegerina, Vitamina D, Osteopontina, Col1A1 e RANK-L entre o grupo de doentes e em controles saudáveis pareados, em T1. O fluido salivar detectou a expressão de todos os cinco marcadores, sendo observado diferença estatística para Osteoprotegerina (p <0,0001), Vitamina D BP (p = 0,0274) e TRANCE/RANK L (p <0,0001). Ademais, a correlação entre a expressão salivar e sérica, no próprio grupo de doentes, evidenciou diferença estatística significativa em todos os marcadores (p <0,0001), com exceção ao TRANCE/RANK L (p <0,9421). A aferição de alterações ósseas, por meio do índice mandibular cortical, mostrou-se associada à densidade mineral óssea vertebral e femoral, sugerindo o papel da radiografia panorâmica como indicador de modificações da massa óssea, sendo uma ferramenta auxiliar à diagnose; porém, não substituível à densitometria óssea. A saliva mostrou-se como uma alternativa biológica aos demais fluidos corporais, na detecção de alterações sistêmicas pertinentes ao metabolismo ósseo, resultantes da corticoterapia crônica, em indivíduos com pênfigo vulgar.

Cytokeratin immunoprofile of primary and metastatic adenoid cystic carcinoma of salivary glands: a report of two cases

Distant metastases from salivary gland tumors are considered infrequent: the incidence of distant metastases ranges from 24% to 61% according to different histotypes and to the site of the primary mass. The most common site of distant metastases due to salivary gland malignancies is the lung. From the pathology point of view, cytokeratins (CK) are important differentiation markers in salivary gland tumors, which are often used for the diagnostic process. Their employment also may be useful to identify and confirm the diagnosis of their distant metastases. We report the expression of CK in two cases of primary and metastatic adenoid cystic carcinoma (ACC) and their CK profiles of the primary and metastatic masses. Both patients-one male and one female-were diagnosed with an ACC cribriform and tubular, respectively, with lung metastases. In case 1, the metastatic mass presented the same histotype and CK profile of the primary tumor. For case 2, the metastatic lung mass was distinct from the primary mass (a solid ACC) and presented a different CK profile. Although salivary gland metastatic disease presents a poor prognosis, both patients reported herein are alive despite the presence of the disease in long-term follow-up. Therefore, the modifications seen in the CK profiles do not appear to be predictive of tumor behavior and outcome. The use of a CK profile seems to be useful to identify the nature of a distant mass and its possible correlations with a primary salivary gland tumor.

Cytokeratin immunoprofile of primary and metastatic adenoid cystic carcinoma of salivary glands: a report of two cases.

Distant metastases from salivary gland tumors are considered infrequent: the incidence of distant metastases ranges from 24% to 61% according to different histotypes and to the site of the primary mass. The most common site of distant metastases due to salivary gland malignancies is the lung. From the pathology point of view, cytokeratins (CK) are important differentiation markers in salivary gland tumors, which are often used for the diagnostic process. Their employment also may be useful to identify and confirm the diagnosis of their distant metastases. We report the expression of CK in two cases of primary and metastatic adenoid cystic carcinoma (ACC) and their CK profiles of the primary and metastatic masses. Both patients-one male and one female-were diagnosed with an ACC cribriform and tubular, respectively, with lung metastases. In case 1, the metastatic mass presented the same histotype and CK profile of the primary tumor. For case 2, the metastatic lung mass was distinct from the primary mass (a solid ACC) and presented a different CK profile. Although salivary gland metastatic disease presents a poor prognosis, both patients reported herein are alive despite the presence of the disease in long-term follow-up. Therefore, the modifications seen in the CK profiles do not appear to be predictive of tumor behavior and outcome. The use of a CK profile seems to be useful to identify the nature of a distant mass and its possible correlations with a primary salivary gland tumor.

Utilização de guias cirúrgicas para colocação de implantes dentários: revisão de literatura / The use of surgical guides for dental implant placement: literature review

Objetivo: esse trabalho pretendeu, por meio de uma revisão de literatura, evidenciar a literatura existente que abordou o tema de guias cirúrgicas utilizadas na implantodontia. Materiais e Métodos: pela revisão de literatura, foi possível abordar o tema com relatos de caso, outras revisões de literatura, estudos in vitro e estudos in vivo com pacientes. Sabemos também que diferentes tipos de guias cirúrgicas foram utilizadas, como as dento-suportadas, muco-suportadas e as apoiadas em osso. Os estudos avaliaram a precisão na colocação do implante utilizando a tomografia computadorizada para colocação virtual do implante, por meio de softwares, e comparando com a tomografia obtida após a colocação do implante. Dessa maneira, os estudos avaliaram a posição do implante no nível coronário e apical, bem como o desvio angular deste. Pelos resultados, pode-se perceber que a precisão e acurácia na colocação dos implantes é maior nos estudos in vitro em relação aos estudos in vivo clínicos. Conclusão: a utilização de guias cirúrgicas pode ser um grande avanço na tecnologia de colocação de implantes dentários, no entanto, mais estudos com maior critério de evidência científica devem ser conduzidos para que a utilização das guias seja melhor sustentada cientificamente.

Objective: The objective of this study was, based on a literature review, evidenciate the literature that approached the subject surgical guides in dental implants. Materials and Methods: it was possible, through the literature review, introduce the subject with case reports, another literature reviews, in vitro studies and in vivo clinical studies. Different types of surgical guides were evaluated, as supported by teeth, muco-supported and bone fixed. The studys evaluated the precision at the dental virtual implant positioning, using the computed tomography, using softwares, and comparing with the computed tomography obtained after the implant placement – the factual implant, and using a software, compare the virtual implant with the factual implant. In this course, studys evaluated the position of the implant at coronal and apical level, and the angular deviation. Based on the studys results, the implant position is more accurate at in vitro studys, compared to the in vivo studys. Conclusion: The use of surgical guides can be a enourmous advance in technology at the dental implant instalation, although more studys with a major critery of scientific evidence must be conducted for the surgical guide more scientific sustentaion useness.

Análise clínica, histopatológica e imunoistoquímica comparativa do fenótipo de tumores primários e tumores metastáticos de glândulas salivares / Clinical and phenotypical analysis of primary and metastatic salivary glands neoplasms: cytokeratins profile

Apesar da incidência relativamente baixa, as neoplasias de glândulas salivares (NGSs) constituem um grupo de doenças caracterizado pela notável heterogeneidade em sua apresentação clínica, histológica e comportamento biológico, abrigando um fator de extrema relevância a despeito de seu prognóstico: a ocorrência de metástases, considerada a principal intercorrência relacionada à mortalidade em pacientes oncológicos. Neste estudo, analisamos as características clínicas e histopatológicas de pacientes diagnosticados com metástases à distância de carcinomas de glândulas salivares tratados no A.C. Camargo Cancer Center, São Paulo, no período de 1970 a 2010. Investigamos alterações fenotípicas entre os tumores primários e tumores metastáticos de glândulas salivares, a partir do estudo da caracterização do padrão de expressão de citoqueratinas, procurando identificar a associação entre a expressão destes antígenos a fatores de risco, ou não, ao potencial metastático à distância e sua importância prognóstica. A casuística total compreendeu 43 pacientes diagnosticados com metástase à distância, com a média de idade de 42.5 anos sendo a glândula parótida o órgão primário mais acometido, e os pulmões o sítio metastático mais incidente. O tipo histológico mais comumente relacionado à metástase foi o carcinoma adenoide cístico. A análise imunoistoquímica da expressão de citoqueratinas fora realizada em 10 neoplasias primárias e 10 metastáticas, as quais revelaram um padrão fenotípico similar no tumor primário e no tumor metastático, apresentando a evidenciação majoritária de células luminais de estruturas ductais. A perda de expressão dos marcadores em áreas tumorais periféricas, adjacentes ao parênquima pulmonar, corrobora a predição de alteração do citoesqueleto das células neoplásicas, possivelmente promovendo uma maior capacidade de migração das células neoplásicas.

Salivary gland neoplasms consist of a notorious group of malignancies best known for its clinical features, biological behavior and histological heterogeneity. An important facto related to prognosis is distant metastasis (uncommon in salivary gland tumors). Cytokeratins (CK) are important differentiation markers frequently used for diagnosis processes. Its employment may be useful to identify metastatic disease. In this study, a retrospective evaluation was performed on patients undergoing treatment for metastatic salivary glands tumors between 1970 and 2010, from A.C. Camargo Cancer Center, São Paulo, Brazil. Demographic data and histopathological specimens were obtained from the medical records. Investigation of the expression of cytokeratins in primary and metastatic salivary gland neoplasms was performed and correlated with their phenotypical patterns. Forty three eligible patients were obtained from the database. Parotid gland represented the primary tumor site most frequently related to metastasis. Lung was the most common metastatic site. Adenoid cystic carcinoma was the histological type more frequently associated to metastatic disease. Immunohistochemistry analysis was performed in 10 primary salivary gland tumors and 10 metastatic salivary gland neoplasms. CK expression patterns were similar in both primary and metastatic neoplams, except for the tumor periphery in close contact with lung parenchyma. Cytokeratins were absent in the invasive front of metastatic lesions, and this may be related to an increased capacity of tumor cells migration and proliferation.