MMP13 Expression and Activity Suggest Its Role in Bone Resorption in Ameloblastomas.

BACKGROUND: Ameloblastoma is a locally destructive benign odontogenic tumor. While the neoplastic cells of conventional ameloblastoma can infiltrate the connective tissue and bone, in unicystic ameloblastoma the epithelium is encapsulated. The mechanisms driving ameloblastoma's bone resorption remains unclear. METHODS: RNA sequencing (RNA-seq) was performed in a discovery cohort of conventional ameloblastoma, and pathway enrichment analysis was carried out. mRNA levels of MMP13, a gene associated with bone resorption, were assessed using RT-qPCR in a larger cohort of conventional ameloblastoma and in unicystic ameloblastoma. Zymogram gels and the immunoexpression profile of collagenase 3 (encoded by MMP13 gene) were evaluated as well. RESULTS: Enriched pathways related to bone mineralization and upregulation of MMP13 were observed in ameloblastomas. Collagenolytic activity of collagenase 3 was detected in the tumor lysates. Collagenase 3 immunopositivity was observed in ameloblastomatous epithelium infiltrating the fibrous capsule of unicystic ameloblastoma. At the tumor-bone interface, collagenase 3 expression was detected in stromal cells, osteoblasts, and osteocytes. CONCLUSION: The results indicate a potential involvement of MMP13 in ameloblastoma-related bone resorption and progression.

EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features.

The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.

EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features

Abstract The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.

Immunohistochemical expression of EGFR in oral leukoplakia: association with clinicopathological features and cellular proliferation.

OBJECTIVES: To investigate the immunoexpression of epidermal growth factor receptor (EGFR) in a sample of oral leukoplakias (OL) and to determine the receptor' s association with dysplasia, tobacco consumption, lesion site, and proliferation rate. Although EGFR should be overexpressed in some oral leukoplakias, the factors that may interfere with this expression and the influence of this receptor on epithelial proliferation have yet to be investigated. STUDY DESIGN: Samples of oral leukoplakias (48) and of normal oral epithelium (10) were immunohistologically examined for expression of EGFR. Immunohistochemistry for Ki-67, and p27 were also performed in leukoplakias. EGFR expression was associated with clinical and pathological features. RESULTS: EGFR was positive in 62.5% of the leukoplakias and 50% of normal oral epithelium. The number of EGFR positive OL located in high-risk sites was significantly higher than EGFR positive OL located in low-risk sites. Most of the p27 negative leukoplakias were EGFR positive, and the p27 index in the parabasal layer was diminished in the presence of dysplasia. Positivity for EGFR was not associated with dysplasia, tobacco exposure, or Ki-67. CONCLUSION: EGFR is expressed in leukoplakia regardless of dysplasia, but EGFR positivity should be more frequent in lesions sited in areas of high cancer risk. The association between EGFR and p27 may represent an important mechanism in the control of cellular proliferation and malignant progression of oral epithelium and therefore warrants further investigation.

Loss of heterozygosity of the PTCH gene in ameloblastoma.

Ameloblastoma is a locally aggressive benign neoplasm derived from odontogenic epithelium, with high recurrence rates. Alterations in the Sonic Hedgehog signaling pathway, including PTCH gene mutations, have been associated with the pathogenesis of some odontogenic tumors. The purpose of the present study was to assess loss of heterozygosity at the PTCH locus in ameloblastoma. Twelve ameloblastomas were included, and loss of heterozygosity was assessed by using 3 microsatellite markers D9S252, D9S127, and D9S287 and 3 single-nucleotide polymorphisms rs112794371, rs111446700, and rs357564, all located at the PTCH gene locus. Furthermore, we investigated GLI1 and GLI2 transcription levels by quantitative reverse transcription polymerase chain reaction in 8 ameloblastomas and, concomitantly, PTCH protein levels by immunohistochemical analysis. Loss of heterozygosity at 9q21.33-9q.31 was detected in 4 (40.0%) of 10 informative cases of ameloblastoma. All 8 analyzed samples expressed GLI1 messenger RNA and 7 cases GLI2 messenger RNA. Interestingly, loss of heterozygosity at the PTCH locus was not correlated with GLI1 or GLI2 transcription levels, nor was there any correlation with PTCH protein expression. In conclusion, our findings suggest that loss of heterozygosity in the PTCH region may be relevant to the pathogenesis of ameloblastoma but may target a different gene than PTCH.

Carcinoma de células escamosas de boca: relação entre graduação histopatológica e características clínicas da neoplasia / Oral squamous cell carcinoma: relation between histopathologic graduation and clinical features of the neoplasia

As características histopatológicas do carcinoma de células escamosas de boca (CCEB) têm sido utilizadas para previsão do comportamento clínico desta neoplasia. Objetivo: Descrever as características de uma amostra de CCEB e verificar a relação da graduação histopatológica com características do indivíduo e da lesão, procurando identificar associações relacionadas com o comportamento agressivo desta neoplasia. Métodos: O protocolo foi aprovado pelo Comitê de Ética em Pesquisa da UFMG. Todos os casos selecionados foram de CCEB diagnosticados no serviço de Patologia Bucal da Faculdade de Odontologia da UFMG e no serviço de Estomatologia do Hospital Municipal Odilon Behrens. A amostra compreendeu 72 casos de CCEB, sendo 56 homens e 16 mulheres. Os indivíduos foram submetidos a questionários quanto aos seus hábitos tabagista e etilista, tempo de evolução da lesão e sintomatologia. Foram realizados exames clínicos, e os fragmentos tumorais foram revisados e graduados através do método proposto por Bryne et al. (1989). Os dados foram analisados, pelo teste do Qui-quadrado, no software SPSS 12.0 (p menor que 0,05). Resultados: Os tumores foram graduados como 23 bem diferenciados (32%), 23 moderadamente diferenciados (32%) e 26 mal diferenciados (36%). Neoplasias histologicamente mais agressivas foram mais frequentemente localizadas em língua ou assoalho bucal, sem, entretanto diferença estatisticamente significante (p maior que 0,05). A maioria das lesões mal diferenciadas (15 / 71,4%) exibiu metástase regional e o envolvimento linfonodal mostrou associação com tamanho da lesão (p menor que 0,05). Conclusão: Os resultados sugerem que algumas características da neoplasia, tais como, tamanho do tumor, sua localização (língua e/ou assoalho bucal), bem como a ocorrência de metástases para linfonodos locais, podem estar relacionados com a agressividade histológica do CCEB.

The histopathological characteristics of oral squamous cell carcinoma (OSCC) have been used to predict the clinical behavior of this neoplasia. Purpose: The aim of this study was describe the characteristics of an OSCC sample and verify the relation between histological grading and characteristics of the subjects and the tumor, identifying associations with the aggressive behavior of this lesion. Method: The protocol of this study was approved by the Research Ethics Committee from Universidade Federal de Minas Gerais (COEP-UFMG). OSCC cases selected were diagnosed in Oral Diagnosis Service at the Dentistry School of UFMG and in Odilon Behrens Hospital. ). The sample consisted of 72 patients with OSCC, been 56 men and 16 women. The patients were submitted to a questionnaire about tobacco and alcohol habits, evolution time and symptomatology. Clinical examinations were performed and tumor fragments were reviewed and graded in accordance to the criteria proposed by Bryne et al. (1989). The data were analyzed in SPSS (Statistic Package for Social Sciences) 12.0 for Windows (p less than 0,05). Results: Twenty-three tumors were graded histologically as well differentiated (32%), 23 moderately differentiated (32%) and 26 poorly differentiated (36%). Neoplasms histologically more aggressive were often located in tongue and floor of mouth, however, without statistical significance (p greater than 0,05). The majority of the well differentiated lesions (71,4%) exhibited regional metastasis and the lymph node involvement showed association with tumor's size (p less than 0,05). Conclusion: The results suggest that histological aggressiveness could be associated with size and regional dissemination in OSCC and that tumors located in tongue and floor of mouth may exhibit more aggressive behavior.

Lesão liquenóide oral relacionada ao amálgama / Amalgam-related oral lichenoid lesion

A lesão liquenóide oral relacionada ao amálgama, condição rara na prática odontológica, constitui importante diagnóstico diferencial no grupo das leucoplasias orais. Relatam-se dois casos que apresentaram rápida resolução clínica após a substituição das restaurações de amálgama.

Amalgam-related oral lichenoid lesion, a rare disorder in dental practice, is an important differential diagnosis among oral leukoplastic lesions. We report two cases with rapid clinical resolution following the replacement of amalgam fillings.