Immunoexpression of HSP27 does not seem to influence the prognosis of oral tongue squamous cell carcinoma

Abstract New methods of early detection and risk assessment have been studied aiming to predict the prognosis of patients and directing a specialized treatment of the oral tongue squamous cell carcinoma (OTSCC). In this context, several molecular biomarkers have been investigated for this purpose, and, among them, the heat shock protein 27 (HSP27) can be named. The study aimed to analyze whether heat shock protein 27 (HSP27) exerts any influence on OTSCC, correlating its immunoexpression with clinicopathological parameters, and patient survival. The sample comprised 55 OTSCC cases and 20 normal oral mucosa specimens. The malignancy grading systems proposed by the WHO in 2005, Brandwein-Gensler et al., and Almangush et al. were applied in a histomorphological study. HSP27 expressions were evaluated through the Immunoreactivity Score System (IRS). Significant values were considered at p <0.05 for all statistical tests. Higher IRS results were observed for normal oral mucosa specimens when compared to OTSCC cases (p <0.001). No significant associations between HSP27 immunostaining, the analyzed clinicopathological parameters and patient survival were observed. The results of the present study indicate lower HSP27 expression in OTSCC cases compared to normal oral mucosa specimens. Thus, HSP27 expression does not seem to influence patient prognosis.

Resumo Novos métodos de detecção precoce e avaliação de risco estão sendo estudados com o intuito de predizer o prognóstico dos pacientes e direcionar um tratamento diferenciado. Neste contexto, vários biomarcadores moleculares têm sido investigados com esta finalidade, dentre eles a heat shock protein 27 (HSP27). Esta pesquisa objetivou analisar se a HSP27 exerce alguma influência nos carcinomas de células escamosas de língua oral (CCELO), correlacionando a sua imunoexpressão com parâmetros clinicopatológicos e com a sobrevida dos pacientes. A amostra foi constituída por 55 casos de CCELO e 20 espécimes de mucosa oral normal. Os sistemas de gradação de malignidade propostos pela OMS em 2005, Brandwein-Gensler et al. e Almangush et al. foram aplicados em um estudo histomorfológico. A expressão da HSP27 foi avaliada através do Sistema de Escore de Imunorreatividade (IRS). Para todos os testes estatísticos foram considerados valores significativos com p<0,05. Foi observado um maior IRS para a mucosa oral normal quando comparado aos casos de CCELO (p<0,001). Não foram encontradas associações significativas entre a imunomarcação da HSP27 com os parâmetros clinicopatológicos analisados e com a sobrevida dos pacientes. Os resultados do presente estudo indicam uma menor expressão da HSP27 nos casos de CCELO quando comparados aos espécimes de mucosa oral normal. Assim, a expressão da HSP27 parece não influenciar o prognóstico dos pacientes.

EGFR, VEGF, and angiogenesis promote the development of lipoma in the oral cavity

Abstract This study aimed to detect, quantify and compare the immunohistochemical expression of EGFR and VEGF and microvessel count (MVC) in oral lipomas, and to correlate the findings with clinical and morphological characteristics of the cases studied. The sample consisted of 54 oral lipomas (33 classic and 21 non-classic) and 23 normal adipose tissue specimens. Cytoplasmic and/or nuclear immunohistochemical staining of EGFR and VEGF was analyzed. The angiogenic index was determined by MVC. Cells were counted using the Image J® software. The Statistical Package for the Social Sciences was used for data analysis, adopting a level of significance of 5% for all statistical tests. A statistically significant difference in EGFR immunoexpression (p=0.047), especially, between classic lipomas and normal adipose tissue. There was a significant difference in MVC between non-classic lipomas and normal adipose tissue (p=0.022). In non-classic lipomas, only VEGF immunoexpression showed a significant moderate positive correlation (r=0.607, p=0.01) with MVC. In classic lipomas, the number of EGFR-immunostained adipocytes was directly proportional to the number of VEGF-positive cells, demonstrating a significant moderate positive correlation (r=0.566, p=0.005). The results suggest that EGFR, VEGF, and angiogenesis participate in the development of oral lipomas but are not primarily involved in the growth of these tumors.

Resumo Lipomas são as neoplasias mesenquimais benignas mais comuns, no entanto sua etiopatogenia ainda permanece desconhecida. Dessa forma, essa pesquisa teve como objetivo detectar, quantificar e comparar a expressão imunoistoquímica do EGFR, VEGF e contagem microvascular (MVC) dos lipomas orais, relacionando-os com as características clínicas e morfológicas dos casos estudados. A amostra foi composta por 54 lipomas orais (33 clássicos e 21 não clássicos) e 23 casos de tecido adiposo normal. A análise da expressão imunoistoquímica de EGFR e VEGF foi fundamentada na marcação citoplasmática e/ou nuclear. O índice angiogênico foi avaliado por meio da MVC. A contagem de células foi realizada utilizando software IMAGE J®. Os dados obtidos foram analisados no software Statistical Package for Social Science. O nível se significância de 5% foi adotado para os testes estatístico. A análise da imunoexpressão das proteínas revelou para o EGFR diferença estatisticamente significativa (p=0,041) entre o lipoma clássico e o tecido adiposo normal. Houve diferença significativa na MVC entre lipomas não clássicos e tecido adiposo normal (p=0,022). Nos lipomas não clássicos, apenas a imunoexpressão de VEGF apresentou correlação do tipo moderada, positiva e significativa (r=0,607; p=0,010) em relação a MVC. Ademais, nos lipomas clássicos foi percebido que os adipócitos imunomarcados para EGFR estiveram diretamente proporcionais a imunoexpressão de VEGF, apresentando correlação do tipo moderada, positiva e estatisticamente significativa (r=0,566; p = 0,005). Com base nos resultados, pode-se sugerir que o EGFR, VEGFR e MCV participam do desenvolvimento nos lipomas orais, contudo, não estão primariamente envolvidos no crescimento tumoral dessas neoplasias.

Immunohistochemical analysis of SHH, SMO and GLI-1 proteins in epithelial odontogenic lesions

Abstract The present study analyzed the expression of proteins involved in the sonic hedgehog signaling pathway (SHH, SMO, and GLI-1) in benign epithelial odontogenic lesions (odontogenic keratocyst - OKC, ameloblastoma - AB, and adenomatoid odontogenic tumor - AOT) in order to identify the role of these proteins in the pathogenesis of these lesions. The sample consisted of 20 OKCs, 20 ABs, and 10 AOTs. The Kruskal-Wallis, Mann-Whitney U, and Spearman's (r) tests were used for statistical analysis, with the level of significance set at 5% (p < 0.05). The membrane/cytoplasmic expression of SHH was significantly higher in AB compared to AOT (p = 0.022) and OKC (p = 0.02). No differences were found in the membrane/cytoplasmic expression of SMO between the lesions studied. Regarding GLI-1, significant differences were observed at the nuclear level for AB and OKC compared to AOT (p < 0.0001). In addition, significant positive correlations were found between cytoplasmic and nuclear GLI-1 in AB (r = 0.482; p = 0.031) and OKC (r = 0.865; p < 0.0001), and between membrane/cytoplasmic SMO and cytoplasmic GLI-1 in AOT (r = 0.667; p = 0.035) and OKC (r = 0.535; p = 0.015). The results of this study confirm the participation of the sonic hedgehog signaling pathway in the pathogenesis of the lesions studied. Overexpression of SHH in ABs and nuclear expression of GLI-1 in ABs and OKCs indicate that these proteins contribute to the more aggressive behavior of these two lesions when compared to AOT.

Resumo O presente estudo analisou a expressão de proteínas envolvidas na via de sinalização Sonic Hedgehog (SHH, SMO e GLI-1) em lesões benignas do epitélio odontogênico de comportamento biológico distintos, tais como ceratocistos odontogênicos (CO), ameloblastomas (AMB) e tumores odontogênicos adenomatoides (TOA), com o intuito de identificar o papel destas proteínas na patogênese destas lesões. A amostra foi constituída de 20 CO, 20 AMB e 10 TOA, analisada pela técnica da imuno-histoquímica de forma semiquantitativa por compartimento celular, onde foi feita uma análise da membrana e citoplasma das células nas proteínas SHH e SMO, enquanto que para a proteína GLI-1, foi feita uma análise nuclear e/ou citoplasmática. Para análise estatística, foram utilizados os testes de Kruskal-Wallis (KW), Mann-Whitney (U) e Spearman (r), com o nível de significância estabelecido em 5% (p < 0,05). Ao analisar a proteína SHH, observou-se que o AMB demonstrou expressão membranar/citoplasmática significativamente maior em comparação ao TOA (p = 0,022) e CO (p = 0,020). Com relação à análise membranar/citoplasmática da SMO, não foram identificadas diferenças entre as lesões estudadas. Para a proteína GLI-1, foram constatadas diferenças estatisticamente significativas, em nível nuclear, para o AMB e CO em comparação ao TOA (p< 0,0001). Além disso, foram observadas correlações positivas com significância estatística entre GLI-1 citoplasmático e GLI-1 nuclear para o AMB (r = 0,482; p = 0,031) e CO (r = 0,865; p< 0,0001), e entre o SMO membranar/citoplasmático e o GLI-1 citoplasmático para o TOA (r = 0,667; p = 0,035) e o CO (r = 0,535; p = 0,015). Os resultados deste estudo confirmam a participação da via de sinalização Sonic Hedgehog na patogênese das lesões estudadas e, a superexpressão de SHH em AMBs e GLI-1 nuclear em AMBs e COs, indica que estas proteínas contribuem com o comportamento biológico mais agressivo destas duas lesões quando comparado ao TOA.

Differential protein expression of osteoclastogenic factors in odontogenic cysts and tumors

Abstract: The osteolytic activity of odontogenic cysts and tumors is directly associated with their growth and aggressiveness. The influence of proteins expressed by epithelial and mesenchymal cells on this biological event differs between indolent cystic lesions, aggressive cystic lesions, and odontogenic tumors. The objective of this study was to compare the immunohistochemical expression of factors that stimulate (receptor activator of nuclear factor kappa-Β ligand - RANKL, cathepsin K - CatK and matrix metallopeptidase 8 - MMP-8) and inhibit (osteoprotegerin - OPG) osteoclastogenesis between dentigerous cyst (DC), glandular odontogenic cyst (GOC), odontogenic keratocyst (OKC), and ameloblastoma (AB). Paraffin-embedded sections of nine DCs, nine GOCs, 20 OKCs, 21 ABs, and four dental follicles (DFs) were subjected to immunohistochemistry. Immunoreactivity was analyzed semiquantitatively and quantitatively in epithelium and connective tissue, respectively. The proteins were immunoexpressed in epithelial and mesenchymal cells of all lesions studied. The expression of RANKL and CatK was higher in OKC, AB, and GOC (p<0.005). Higher expression of OPG was found in DF and DC compared to the other markers (p<0.005). MMP-8 expression was high in GOC and OKC. This study demonstrated the differential expression of factors that inhibit and stimulate bone resorption during the development of DC, GOC, OKC, and AB. Higher expression of RANKL and CatK was observed in more aggressive lesions. OPG appears to be one of the molecules responsible for the slower growth of DC.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma

Abstract Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Involvement of tryptase-positive mast cells and angiogenesis in the growth of inflammatory odontogenic cysts

Abstract: Inflammatory periapical lesions are characterized by infiltration of different immune cell types, the functions of which depend on an effective vascular network. This study aimed to evaluate the mast cells density (MCD) in inflamatory odontogenic cysts capsules concerning microvascular density (MVD), microvascular area (MVA), and microvascular perimeter (MVP), and correlate such findings with the type of lesion, intensity of the inflammatory infiltrate, and thickness of the epithelial lining. Twenty inflamatory dentigerous cysts (IDCs), twenty radicular cysts (RCs), and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-tryptase and anti-CD34 antibodies. RCs exhibited the highest MCD, MVD, MVA, and MVP indexes (p = < 0.001, p = 0.008, p = 0.003 and p = < 0.001, respectively), and lesions with inflammatory infiltrate grade III showed the highest MVD (p = 0.044). Considering epithelial thickness, a higher MVP index was identified in lesions with hyperplastic epithelium (p = 0.018). In IDCs, RCs, and RRCs, a strong positive correlation was observed between MVA and MVP (r = 0.950 and p = < 0.001; r = 0.914 and p = < 0.001; r = 0.713 and p = < 0.001, respectively). In IDCs, a moderate correlation was observed between MCD and both MVA and MVP (r = 0.660 and p = 0.002; r = 0.634 and p = 0.003, respectively). These results suggest that tryptase-positive mast cells might play an important role in the angiogenic activity of IDCs, while RCs had the highest indexes. Our findings also confirmed that the intensity of the inflammatory infiltrate and epithelial thickness influence angiogenesis.

Extensive central ossifying fibroma of mandible: case report / Extenso fibroma ossificante central em mandíbula: relato de caso

ABSTRACT A 34-year-old female patient attended a referral center for oral diagnosis presenting hardened increased volume in the posterior mandible. Panoramic radiography revealed a mixed unilocular lesion with clear and well-defined limits. The incisional biopsy showed proliferation of mesenchymal cells amid dense fibrous connective tissue. Mineralized material in different degrees of maturation was also observed. Regarding the histopathological aspects associated with the clinical, radiographic, and intraoperative data, the diagnosis of central ossifying fibroma (COF) was performed. COF has similar characteristics to other fibro-osseous lesions, and its diagnosis is a challenge for dental surgeons.

RESUMEN Paciente de 34 años de edad, acudió a un centro de referencia odontológico con aumento de volumen endurecido en la mandíbula posterior. La radiografía panorámica reveló lesión unilocular mixta, de límites precisos y definidos. La biopsia incisional demostró una proliferación de células mesenquimales en medio de un tejido conectivo fibroso denso. Aún se observó material mineralizado en diferentes grados de maduración. Considerando la histopatología, asociada a los datos clínicos, radiográficos y transquirúrgicos, el diagnóstico de fibroma osificante central (FOC) se reveló. El FOC presenta características similares a las de otras lesiones fibro-óseas, y su diagnóstico es un desafío para los cirujanos dentales.

RESUMO Paciente do sexo feminino, 34 anos, compareceu a um centro de referência em diagnóstico oral apresentando aumento de volume endurecido em mandíbula posterior. A radiografia panorâmica revelou lesão unilocular mista, de limites precisos e definidos. A biópsia incisional evidenciou uma proliferação de células mesenquimais em meio a um tecido conjuntivo fibroso denso. Foi observado ainda material mineralizado em diferentes graus de maturação. Considerando os aspectos histopatológicos, associados aos dados clínicos, radiográficos e transcirúrgicos, o diagnóstico de fibroma ossificante central (FOC) foi revelado. O FOC apresenta características similares às de outras lesões fibro-ósseas, e seu diagnóstico é um desafio para os cirurgiões-dentistas.

Benign neural lesions of the oral and maxillofacial complex: a 48-year-retrospective study / Lesões neurais benignas do complexo bucomaxilofacial: estudo retrospectivo de 48 anos

ABSTRACT Introduction: Peripheral nerve sheath lesions are among the various diseases that can affect the nervous tissue. These neural origin lesions may occur in the maxillofacial region, although they are rare. Objective: The aim of this study was to retrospectively evaluate patient's profiles presenting benign neural tumors of the oral and maxillofacial complex and carry out comparisons with previous studies. Methods: A descriptive and retrospective study of the clinical records of patients diagnosed with benign oral and maxillofacial neural lesions at the Department of Dentistry of the Universidade Federal do Rio Grande do Norte (UFRN) was carried out, from 1970 to December 2017. Results: From a total of 15,527 histopathological records analyzed over 48 years, 57 (0.37%) corresponded to benign neural lesions, of which 24 (42.11%) were neurofibroma, 15 (26.32%) were traumatic neuroma, nine (15.79%) were neurilemoma, three (5.26%) were granular cell tumor, three (5.26%) were congenital epulis, and three (5.26%) were solitary circumscribed neuroma. Three patients (12.5%) with neurofibroma also presented type I neurofibromatosis. Most patients were female (56.66%), ranging in age from three days to 79 years old. Conclusion: The data obtained confirmed that lesions of neural origin are uncommon in the oral cavity and that neurofibroma is the most frequent, female are the most affected, and the tongue is the most prevalent affected area.

RESUMEN Introducción: Las lesiones nerviosas periféricas son algunas de las varias enfermedades que pueden afectar el tejido nervioso. Esas lesiones de origen neural pueden ocurrir en la región maxilofacial, aunque sean raras. Objetivo: El objetivo de este estudio fue evaluar retrospectivamente el perfil de pacientes con tumores neurales benignos del complejo oral y maxilofacial y realizar comparaciones con estudios previos. Método: Se trata de un estudio retrospectivo y descriptivo de los historiales de pacientes con diagnóstico de lesiones benignas neurales del área oral y maxilofacial del Departamento de Odontología de la Universidade Federal do Rio Grande do Norte (UFRN), desde 1970 hasta 2017. Resultados: Se analizaron 15.527 registros histopatológicos en 48 años; 57 (0,37%) correspondieron a lesiones neurales benignas, con 24 (42,11%) neurofibromas, 15 (26,32%) neuromas traumáticos, nueve (15,79%) neurilemomas, tres (5,26%) compuestos por tumores de células granulares, tres (5,26%) épulis congénitos y tres (5,26%) neuromas circunscritos solitarios. Tres pacientes (12,5%) con neurofibroma también presentaron neurofibromatosis tipo I. La mayor parte de los pacientes era del sexo femenino (56,66%), con edades comprendidas entre los 3 días y los 79 años. Conclusión: Los dados obtenidos confirmaron que tumores de origen neural son poco comunes en la cavidad oral y que los neurofibromas son los más frecuentes, mientras que el sexo femenino es el más afectado y la lengua, el sitio anatómico más prevalente.

RESUMO Introdução: As lesões nervosas periféricas estão entre as várias doenças que podem afetar o tecido nervoso. Essas lesões de origem neural podem ocorrer na região maxilofacial, embora sejam raras. Objetivo: O objetivo deste estudo foi avaliar retrospectivamente o perfil de pacientes com tumores neurais benignos do complexo bucomaxilofacial e realizar comparações com estudos prévios. Métodos: Trata-se de um estudo retrospectivo e descritivo dos prontuários de pacientes com diagnóstico de lesões benignas neurais bucais e maxilofaciais do Departamento de Odontologia da Universidade Federal do Rio Grande do Norte (UFRN), no período de 1970 a dezembro de 2017. Resultados: Foram analisados 15.527 registros histopatológicos em 48 anos; 57 (0,37%) corresponderam a lesões neurais benignas, sendo 24 (42,11%) neurofibromas, 15 (26,32%) neuromas traumáticos, nove (15,79%) neurilemomas, três (5,26%) compostos por tumores de células granulares, três (5,26%) epúlides congênitas e três (5,26%) neuromas circunscritos solitários. Três pacientes (12,5%) com neurofibroma também apresentaram neurofibromatose tipo I. A maioria dos pacientes era do sexo feminino (56,66%), com idade variando de 3 dias a 79 anos. Conclusão: Os dados obtidos confirmaram que lesões de origem neural são incomuns na cavidade bucal e que os neurofibromas são os mais frequentes, sendo o sexo feminino o mais acometido e a língua o sítio anatômico mais prevalente.

Mucoepidermoid carcinoma of the retromolar region: case report / Carcinoma mucoepidermoide em região retromolar: relato de caso

ABSTRACT The present study aimed to report a case of mucoepidermoid carcinoma (MEC), focusing on its clinical-pathological characteristics. At intraoral clinical examination, a nodular lesion was observed in the right pterygomandibular raphe region, with three years of evolution. An incisional biopsy was performed, and the diagnostic hypotheses of salivary gland injury and sialadenitis were considered. Histopathologically, a malignant neoplastic process characterized by the proliferation of epidermoid, intermediate and mucosal cells was observed. The histopathological diagnosis of MEC was emitted. The present case praises the importance of early diagnosis and correct management of this disease, providing a better prognosis for these patients.

RESUMEN Reportamos un caso de carcinoma mucoepidermoide (CME) con enfoque en sus rasgos clinicopatológicos. En la exploración clínica intraoral, se observó una lesión de aspecto nodular en región del rafe pterigomandibular derecho, con tiempo de evolución de tres años. Se realizó una biopsia por incisión, considerándose las hipótesis diagnósticas de lesión de glándula salival y sialadenitis. Histopatológicamente, se observó un proceso neoplásico maligno caracterizado por la proliferación de células epidermoides, intermedias y mucosas. El diagnóstico histopatológico fue de CME. El presente caso destaca la importancia del diagnóstico temprano y del manejo correcto de esa enfermedad, ofreciendo un mejor pronóstico para los pacientes portadores de CME.

RESUMO Relatamos um caso de carcinoma mucoepidermoide (CME) com enfoque em suas características clinicopatológicas. No exame clínico intraoral, observou-se lesão de aspecto nodular em região de rafe pterigomandibular direita, com tempo de evolução de três anos. Biópsia incisional foi realizada, e as hipóteses diagnósticas de lesão de glândula salivar e sialadenite foram consideradas. Histopatologicamente, observou-se um processo neoplásico maligno caracterizado pela proliferação de células epidermoides, intermediárias e mucosas. O diagnóstico histopatológico de CME foi emitido. O presente caso enaltece a importância do diagnóstico precoce e do correto manejo dessa patologia, proporcionado um melhor prognóstico para os pacientes portadores de CME.

Immunohistochemical expression of DNA repair proteins in oral tongue and lower lip squamous cell carcinoma

Abstract The DNA repair system involves genes and proteins that are essential for the maintenance of genome integrity and the consequent control of various cellular processes. Alterations in these genes and proteins play a role in tumor development and progression and might be associated with prognosis. The aims of this study were to analyze the immunoexpression of two DNA repair proteins, XPF and XRCC1, in lower lip squamous cell carcinoma (LLSCC) and oral tongue squamous cell carcinoma (OTSCC), and to investigate possible associations with clinical and histopathological parameters. The immunohistochemical expression of XPF and XRCC1 was analyzed semi-quantitatively in 40 cases each of LLSCC and OTSCC. The chi-squared test or Fisher's exact test, when appropriate, was used to investigate the association between expression of the proteins and clinicopathological characteristics. The cytoplasmic immunoexpression of XPF was high in OTSCC (95% of the cases analyzed) but low in LLSCC (52.5%). Among the clinicopathological parameters evaluated, a statistically significant association was observed between high nuclear expression of XRCC1 and the absence of regional lymph node metastasis in patients diagnosed with OTSCC (p=0.006). The high protein expression of XPF and XRCC1 in OTSCC and LLSCC suggests an important role in the development and progression of these tumors. Our study found an association between high nuclear expression of XRCC1 and the absence of loco-regional metastasis in cases diagnosed as OTSCC, suggesting a role of this protein in tumor progression.

Juvenile ossifying fibroma: series of seven cases focusing on clinical and pathological aspects / Fibroma ossificante juvenil: série de sete casos com enfoque nos aspectos clinicopatológicos

ABSTRACT Juvenile ossifying fibroma (JOF) is an uncommon benign fibro-osseous lesion that affects young individuals and deserves attention because it presents an aggressive clinical behavior and high rates of recurrence. This paper aims to report seven cases diagnosed as JOF - age ranging from 11 to 39 years - in a referral center, correlating our findings with clinical and pathological aspects in the literature. The mandible was the most common location, and in three cases, painful symptoms were reported. Regarding the histopathological findings, the majority of cases exhibited a cellularized pattern, and the trabecular subtype was the most commonly found. Regarding treatment, three cases relapsed, and, in two of them, conservative treatments were performed. Accordingly, knowing the clinical-pathological aspects of JOF is important for the correct diagnosis and the establishment of an appropriate treatment that decreases the high recurrence rate of this lesion.

RESUMEN El fibroma osificante juvenil (FOJ) es una lesión fibro-ósea benigna pocofrecuente que acomete personasjóvenesy merece realce, puespresenta comportamiento clínico agresivo y altas tasas de recidivas. Reportamos siete casos diagnosticados como FOJ - con pacientes entre 11 y 39 anos de edad - en un centro de referencia, relacionando nuestros hallazgos con los aspectos clínicos y patológicos existentes en la literatura. La mandíbula fue la ubicación más común; en tres casos se reportaron síntomas dolorosos. En lo que respecta a los hallazgos histopatológicos, la mayor parte de los casos se mostró altamente celularizada, siendo el subtipo trabecular el más común. En cuanto al tratamiento, de los tres casos que presentaran recurrencia, en dos se realizaron tratamientos conservadores. Ante eso, se resalta la importancia de conocer los aspectos clínicos y patológicos del FOJ para hacer el diagnóstico preciso y establecer un tratamiento adecuado que reduzca el alto índice de recidivas de esa lesión.

RESUMO O fibroma ossificante juvenil (FOJ) é uma lesão fibro-óssea benigna incomum que acomete indivíduos jovens e merece destaque por apresentar um comportamento clínico agressivo e altas taxas de recidivas. Este trabalho tem como objetivo relatar sete casos diagnosticados como FOJ - com variação de idade entre 11 e 39 anos - em um centro de referência, correlacionando nossos achados com os aspectos clinicopatológicos existentes na literatura. A mandíbula foi a localização mais comum; em três casos foi relatada sintomatologia dolorosa. Com relação aos achados histopatológicos, a maioria dos casos exibiu um padrão bem celularizado, sendo o subtipo trabecular o mais encontrado. No que diz respeito ao tratamento, dos três casos que apresentaram recidiva, em dois, foram realizados tratamentos conservadores. Diante disso, ressalta-se a importância do conhecimento dos aspectos clínicos epatológicos do FOJ para a realização de um diagnóstico correto e o estabelecimento de um tratamento adequado que diminua o alto índice de recidivas dessa lesão.

Ameloblastic carcinoma arising from a preexistent ameloblastoma / Carcinoma ameloblástico decorrente de um ameloblastoma preexistente

ABSTRACT Ameloblastic carcinoma (AC) is a rare odontogenic tumor that represents the malignant counterpart of an ameloblastoma. There are few cases of AC in the English-language literature, with only 16 cases arising from preexisting ameloblastomas reported in the last 10 years. Multiple local recurrences of ameloblastomas precede this transformation. In the current report, we describe a case of AC at the posterior maxilla in a 42-year-old female submitted to surgical resection, with three recurrences of ameloblastoma in a period of four years. Imaging exams showed a radiodense mass with cortical bone disruption and maxillary sinus invasion. Histologic analysis demonstrated features of islands and nests of malignant epithelium transformation, atypia, pleomorphic cells, nuclear hyperchromatism, necrosis and desmoplasia. AC represents a rare and challenging histologic diagnosis. Surgical access with adequate hard and soft tissue margins is essential for influencing survival. The description of new cases may reveal, through of treatment and clinical follow-up, characteristics that allow us better understanding of AC behavior.

RESUMEN El carcinoma ameloblástico (CA) es un tumor odontogénico raro que representa el equivalente maligno de un ameloblastoma. Hay pocos casos de CA en la literatura en lengua inglesa: en los últimos 10 años, sólo se reportaron 16 casos originados de ameloblastomas previos. Múltiples recidivas locales de este tumor preceden esa transformación. En este reporte, describimos un caso de CA en región posterior de maxila en una mujer de 42 años de edad, sometida a resección quirúrgica. En un periodo de cuatro años, se produjeron tres recurrencias del ameloblastoma. Exámenes de imagen muestran una masa radiodensa con destrucción cortical e invasión del seno maxilar. El análisis histológico ha revelado islas y nidos característicos de transformación epitelial maligna, atipias, pleomorfismo celular, hipercromatismo nuclear, necrosis y desmoplasia. El diagnóstico histológico del CA representa un raro desafío. El abordaje quirúrgico con ampliación de los márgenes de tejido duro y blando es esencial en la sobrevida del paciente. La descripción de nuevos casos puede revelar, mediante tratamiento y acompañamiento clínico, características que ayuden a comprender mejor el comportamiento del CA.

RESUMO O carcinoma ameloblástico (CA) é um tumor odontogênico raro que representa o equivalente maligno de um ameloblastoma. Existem poucos casos de CA na literatura em inglês: nos últimos 10 anos, foram relatados apenas 16 casos surgidos de ameloblastomas preexistentes. Múltiplas recorrências locais desse tumor precedem essa transformação. Neste relato, descrevemos um caso de CA em região posterior de maxila em uma mulher de 42 anos de idade, submetida à ressecção cirúrgica. Em um período de quatro anos, ocorreram três recidivas do ameloblastoma. Exames de imagem exibiram uma massa radiodensa com destruição da cortical óssea e invasão do seio maxilar. A análise histológica revelou ilhas e ninhos característicos de transformação maligna epitelial, atipias, pleomorfismo celular, hipercromatismo nuclear, necrose e desmoplasia. O CA representa um raro e desafiador diagnóstico histológico. O acesso cirúrgico com ampliação das margens de tecido duro e mole é essencial para o impacto na sobrevida do paciente. A descrição de novos casos pode revelar, por meio do tratamento e do acompanhamento clínico, características que ajudem a entender melhor o comportamento do CA.

Immunohistochemical study of fibronectin, tenascin and type I collagen in tongue and lip carcinomas

AIM: The aim was to compare the immunoexpression of extracellular matrix proteins in squamous cell carcinomas of tongue (SCCTo) and lower lip (SCCLi). METHODS: Eleven SCCTo and 11 SCCLi were selected and examined according to Bryne's method (1998). For immunohistochemical study utilized antibodies to fibronectin, tenascin and type I collagen. Histopathologic and immunohistochemical analysis were performed on the tumor invasive front. RESULTS: All SCCTo were classified in high score malignant grade and all SCCLi in lower score. Fibronectin showed strong immunorreactivity in the peritumoral basement membrane (BM) in 91% of SCCTo and all cases of SCCLi, while in the tumor stroma (TS) all cases of SCCTo and SCCLi had strong intensity. Tenascin had strong expression in BM of 91% cases of SCCTo and 63.4% of SCCLi and in TS had strong expression in 91% cases of SCCTo and 54.6% of SCCLi. Type I collagen demonstrated weak immunoreactivity in the TS of 72.7% cases of SCCTo and 63.4% of SCCLi. CONCLUSION: These results may suggest that the strong expression of fibronectin and tenascin proteins and the weak expression of type I collagen could play a role in the invasive process of oral SCC (AU)

Immunohistochemical Analysis of Cell Proliferation and Bcl-2 Expression in Drug-Induced Gingival Overgrowth

Objective: To compare the rate of cell proliferation and expression of antiapoptotic protein Bcl-2 between drug-induced gingival overgrowth (DIGO) and clinical healthy gingiva (CHG) and to establish associations with histopathological features. Material and Methods: Twenty specimens of DIGO and 20 CHG specimens were submitted to morphological and immunohistochemical analysis by light microscopy. Cell proliferation (Ki-67) and the expression of Bcl-2 were evaluated in epithelial cells and spindle-shaped mononuclear cells of the connective tissue by establishing the labeling index (LI). Results: In epithelial tissue, the mean LI for Ki-67 was 17.2% in DIGO and 21.71% in CHG (p = 0.137). The mean LIs for Bcl-2 in epithelial tissue were 14.67% and 10.24% in DIGO and CHG, respectively (p = 0.026). In connective tissue, DIGO and CHG specimens exhibited low LIs for Ki-67 and Bcl-2, with mean values of less than 0.5% in both groups. No significant differences in the LIs for Ki-67 or Bcl-2 in epithelial tissue were observed according to the degree of collagenization, degree of vascularization and intensity of inflammatory infiltration (p > 0.05). No significant correlations were observed between the LIs for Ki-67 and Bcl-2 (p > 0.05). Conclusion: The present results suggest that the pathogenesis of DIGO does not involve increased proliferation or decreased apoptosis of fibroblasts. On the other hand, the morphological pattern of elongated epithelial cristae observed in DIGO could mainly be due to the inhibition of keratinocyte apoptosis and not to increased proliferation of these cells.

Histochemical and immunohistochemical differences between solitary oral fibroma and fibrous papule of the face

Abstract: Background: The morphological similarities between fibrous papules of the face and multiple sporadic oral fibromas were mentioned long ago and a relationship between them has been reported in the literature. Objective: The aim of this study was to evaluate the participation of mast cells, elastin and collagen in a series of oral fibromas and fibrous papules of the face in order to better understand the possible role of these factors in fibrosis and the formation of these lesions. Methods: Thirty cases of oral fibroma involving the buccal mucosa and 30 cases of fibrous papules of the face were selected. Tissue samples were submitted to picrosirius red staining and immunohistochemistry using anti-elastin and anti-tryptase antibodies. Results: The percentage of tryptase-positive mast cells and expression of elastin were higher in cases of fibrous papules of the face (p < 0.05). In contrast, a higher intensity of collagen deposition was observed in oral fibromas. The results showed mast cell accumulation and higher elastin synthesis in fibrous papules of the face, and mast cell accumulation with higher collagen fiber synthesis in oral fibromas. Conclusion: These findings support the hypothesis that mast cells influence the development and growth of these lesions through different mechanisms.

Mucocutaneous Kaposi's sarcoma in an HIV-positive patient: diagnosis and treatment / Sarcoma de Kaposi mucocutâneo em paciente HIV positivo: diagnóstico e tratamento

ABSTRACT Kaposi's sarcoma (KS) is an endothelial neoplasia caused by infection with the human herpesvirus 8 (HHV-8), and the type associated with the human immunodeficiency virus (HIV) is considered the most aggressive and frequent. This paper reports a case of mucocutaneous KS in a patient not formerly aware of being an HIV bearer. A 38-year-old male patient has sought treatment with multiple oral lesions and one in the skin. Serology was positive for HIV and incisional biopsy diagnosed KS. After 11 months of chemotherapy and antiretroviral therapy, there was complete remission of the skin KS and partial remission of oral lesions.

RESUMO Sarcoma de Kaposi (SK) é uma neoplasia endotelial causada pelo herpes vírus humano tipo 8 (HHV-8), e o tipo associado ao vírus da imunodeficiência humana (HIV) é considerado o mais agressivo e frequente. Relata-se um caso de SK mucocutâneo em indivíduo não anteriormente ciente de ser portador de HIV. Paciente do sexo masculino, 38 anos, procurou atendimento com queixa de múltiplas lesões orais e uma lesão em pele. A sorologia foi positiva para HIV, e a biópsia incisional das lesões teve como diagnóstico SK. Após 11 meses de terapia antirretroviral e quimioterapia, houve remissão completa do SK cutâneo e parcial das lesões orais.

Immunoexpression of HIF-1α and VEGF in Periodontal Disease and Healthy Gingival Tissues

Abstract Hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are proteins that stimulate the proliferation and migration of endothelial cells. These proteins have been described in many pathologic and inflammatory conditions, but their involvement in the development of periodontitis has not been thoroughly investigated. This study compared the immunohistochemical expression of these proteins, involved in angiogenesis and hypoxia, by imunnostained inflammatory and endothelial cells in periodontal disease and healthy gingival tissues. Gingival tissue samples were divided as follows: 30 samples with chronic periodontitis, 30 with chronic gingivitis, and 30 of healthy gingiva. Results were analyzed statistically by the Kruskal-Wallis, Mann-Whitney and Spearman correlation tests (p=0.01). Inflammatory and endothelial cells were found to express these proteins. Periodontitis showed median percentage of HIF-1α-positive cells of 39.6%, 22.0% in cases of gingivitis and 0.9% in the healthy gingiva group (p=0.001). For VEGF, median percentage of immunopositive cells was 68.7% for periodontitis, 66.1% in cases for gingivitis, and 19.2% for healthy gingival specimens (p<0.001). Significant correlation between VEGF and HIF-1α was also observed in healthy gingiva (p<0.001).The increased expression of HIF-1αα and VEGF in periodontitis, compared to gingivitis and healthy gingiva, suggests possible activation of the HIF-1α pathway in advanced periodontal disease. The correlation between HIF-1α and VEGF expression in healthy gingiva suggests a physiological function for these proteins in conditions of homeostasis. In periodontal disease, HIF-1 and VEGF expression may be regulated by other factors, in addition to hypoxia, such as bacterial endotoxins and inflammatory cytokines.

Resumo O fator induzível por hipóxia 1 alfa (HIF-1α) e o fator de crescimento endotelial vascular (VEGF) são proteínas que estimulam a proliferação e a migração de células endoteliais. Estas proteínas têm sido descritas em muitas condições patológicas e inflamatórias, mas o envolvimento dessas no desenvolvimento de periodontite não foi completamente investigado. Este estudo comparou a expressão imunohistoquímica destas proteínas, envolvidas na angiogênese e hipóxia, na doença periodontal e em tecidos gengivais saudáveis por meio de contagem de células inflamatórias e endoteliais imunomarcadas. As amostras de tecido gengival foram divididas da seguinte forma: 30 amostras com periodontite crônica, 30 com gengivite crônica e 30 de gengiva saudável. Os resultados foram analisados estatisticamente pelos testes de Kruskal-Wallis e Mann-Whitney (p=0.01). As células inflamatórias e endoteliais foram positivas para estas proteínas. A porcentagem média de células positivas para HIF-1α foi de 39,6% nos casos de periodontite, 22,0% nos casos de gengivite e de 0,9% no grupo de gengiva saudável (p = 0,001). A porcentagem média de células imunopositivas para o VEGF foi de 68,7% nos casos de periodontite, 66,1% nos casos de gengivite, e 19,2% em espécimes gengivais saudáveis (p<0,001). Correlação significativa entre o VEGF e HIF-1α foi observada em gengival. A expressão elevada do HIF-1α e VEGF em periodontite, comparada a gengivite e gengiva saudável, sugere ativação da via do HIF-1α, na doença periodontal avançada. A correlação entre o HIF-1α e expressão de VEGF na gengiva saudável, sugere uma função fisiológica para estas proteínas em condições de homeostase. Na doença periodontal, a expressão de HIF-1α e VEGF pode ser regulada por outros fatores, além da hipóxia, tais como endotoxinas bacterianas e citocinas inflamatórias.

Collagen IV and laminin expression in squamous cellcarcinomas of lower lip and tongue / Expressão de colágeno IV e laminina em carcinomas de células escamosas de lábio inferior e língua

In this study, the expression of extra cellular matrix proteins was immunohisto chemically studied and compared with the histological grading of squamous cell carcinomas of the lower lip and tongue. Material and Methods: The lower lip carcinomas (n =12) and the tongue carcinomas (n = 12) were histopathologically graded according to Bryne’smethod. The immunohisto chemical technique used specific antibodies for collagen IV and laminin. Histopathological and immunohisto chemical analysis were carried-out at the invasive tumor front. Results: Most of the lower lip carcinomas(91.7%) were classified with lower scores and all tongue carcinomas (100%) with high-grade malignant scores (p < 0.01). Collagen type IV expression was absent in the peri tumoral basement membrane in 50% of lower lip carcinomas and in66. 7% of tongue carcinomas (p = 0.09). Laminin expression was absent in the peritumoral basement membrane in 66.7% of lower lip carcinomas and in 58.3% of tongue carcinomas (p = 0.48). When these two glycoproteins were expressed, they showed alinear, thin and discontinuous pattern and a weak intensity of expression. Conclusion: The high gradem alignancy score of the tongue carcinomas was associated with the pattern of expression of the matrix proteins studied. This suggested that tonguesquamous cell carcinomas have more invasive potential and more aggressive biological behaviorthan the lower lip carcinomas...

Neste estudo, a expressão das proteínas da matriz extracelular foi estuda da imunoisto quimicamente e comparada com a classificação histológica dos carcinomas de células escamosas do lábio inferior e língua. Material e Métodos: Os carcinomas de lábio inferior (n = 12)e os carcinomas de língua (n = 12) foram graduados histopatologicamente de acordo com o método de Bryne. A técnica de imunoistoquímica utilizou anticorpos específicos para colágeno IV e laminina. Análises histopatológica e imunoistoquímica foram conduzidas na frente invasiva tumoral. Resultados: A maioria dos carcinomas de lábio inferior (91,7%) foi classificada em baixo grau e todos os carcinomas de língua (100%) em alto grau de malignidade (p < 0,01). A expressão de colágeno tipo IV estava ausente na membrana basal peri tumoral em 50% dos carcinomas de lábio inferior e em 66,7% dos carcinomas de língua (p = 0,09). A expressão de laminina estava ausente na membrana basal peri tumoral em 66,7%dos carcinomas do lábio inferior e em 58,3% dos carcinomas de língua (p = 0,48). Quando estas duas glicoproteínas foram expressas, mostraram-se comum padrão linear, fino e descontínuo e uma fraca intensidade de expressão. Conclusão: O alto grau de malignidade dos carcinomas de língua associou-se com o padrão de expressão das proteínas de matriz estudadas. Isso sugere que carcinomas de células escamosas de língua têm comportamento biológico mais agressivo e potencial mais invasivo do que os carcinomas de lábio inferior...

Influência dos herpes-vírus na patogênese da doença periodontal / Influence of herpesvirus in pathogenesis of disease periodontal – a review of literature

A etiologia da doença periodontal está estreitamente relacionada à presença de microrganismos patogênicos, principalmente bactérias anaeróbias gram-negativas. Estudos recentes sugerem que os herpes-vírus (HHV) podem estar associados à ocorrência e progressão de diferentes formas da doença periodontal. Diante disso, este trabalho fez uma investigação na literatura em relação à presença dos vírus Epstein-Barr (EBV), Citomegalovírus (HCMV) e Herpes simples (HSV) em pacientes com doença periodontal. A análise dos estudos mostra que estes herpes-vírus podem contribuir para a destruição periodontal através da infecção e replicação viral, liberação de mediadores pró-inflamatórios e citotoxinas, ou como resultado de uma alteração na defesa do hospedeiro. Um número crescente de pesquisas sugere que, dentre os HHVs, o EBV e o HCMV são os que estão mais comumente envolvidos no desenvolvimento da doença periodontal. De acordo com a literatura revisada, embora ainda não tenha sido estabelecida uma relação causal entre a infecção por herpes-vírus e o desenvolvimento da doença periodontal, tem sido destacada uma associação positiva entre ambas.

Immunohistochemical study of macrophages subpopulations associated with squamous cell carcinoma of the tongue, with and without metastasis / Estudo imuno-histoquímico das subpopulações de macrófagos associados a tumores em carcinoma epidermoide de língua, com e sem metástase

ABSTRACT Introduction: Stromal cells interact with tumor cells and play an important role in cancer invasion and metastasis. Tumor-associated macrophages (TAMs) can exhibit M1 phenotype, important immune effector cells, or M2 phenotype, able to suppress the function of M1 macrophages and influence angiogenesis and tissue repair. The CD68 antibody recognizes M1 and M2 macrophages, whereas CD163 antibody is specific only to identify M2 macrophages. Objective: To investigate the presence of TAMs in a number of cases squamous cell carcinoma (SCC) of the tongue by associating it with the occurrence of metastasis. Material and methods: Immunohistochemistry was used to evaluate the immunopositivity for CD68 and CD163 in 27 cases of SCC of the tongue. Results: The percentage of CD68 positive macrophages was higher than CD163 positive macrophages in all specimens studied. Comparing CD163 and CD68 immunostaining in the studied groups, it was observed that cases without metastasis had a higher percentage of CD68 positive cells in relation to CD163 positive cells, which was statistically significant. Conclusion: Considering these results, there was a predominance of M1 macrophages in SCC of the tongue cases without metastasis, suggesting the influence of these cells in clinical behavior of the lesion.

RESUMO Introdução: As células do estroma interagem com as células neoplásicas e desempenham papel importante na invasão e na metástase do câncer. Os macrófagos associados ao tumor (TAMs) podem se apresentar com fenótipo M1, importantes células efetoras, ou fenótipo M2, capazes de suprimir a função dos macrófagos M1 e influenciar na angiogênese e no reparo tecidual. O anticorpo CD68 reconhece os macrófagos M1 e M2, enquanto o anticorpo CD163 é específico para a identificação apenas de macrófagos M2. Objetivo: Investigar a presença dos TAMs em uma série de casos de carcinoma epidermoide (CE) de língua, associando-a à ocorrência de metástase. Material e métodos: A técnica imuno-histoquímica foi utilizada para avaliar a imunopositividade ao CD68 e CD163 em 27 casos de CE de língua. Resultados: A porcentagem de macrófagos CD68 positivos foi maior do que a de macrófagos CD163 positivos em todos os espécimes estudados. Comparando a imunomarcação de CD68 e CD163 nos grupos estudados, verificou-se que nos casos sem metástase havia maior proporção de células CD68 positivas em relação às CD163 positivas, o que foi estatisticamente significativo. Conclusão: Diante desses resultados, observou-se a predominância de macrófagos M1 em casos de CE de língua sem metástase, sugerindo a influência dessas células no comportamento clínico da lesão.