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OBJECTIVE Sclerostin is a glycoprotein that plays a catabolic role in bone and is involved in the regulation of bone metabolism by increasing the osteoclastic bone resorption. In this study, serum sclerostin levels were measured in chronic otitis media (COM) with and without cholesteatoma, assuming that it might have a role in the aetiopathogenesis of bone resorption. METHODS A total of 44 patients with cholesteatomatous COM (cCOM) (n = 22) and non-cholesteatomatous COM (ncCOM) (n = 22) were included in this study, and 26 healthy volunteers without any chronic ear disease problem(s) constituted the control group (n = 26). RESULTS No significant difference was not found in terms of serum iPTH, ALP, and vitamin D levels between ncCOM, cCOM, and the control groups. A significant difference was found in terms of serum sclerostin, Ca, and P levels between ncCOM, cCOM, and the control groups (p<0.05). Serum sclerostin levels in the study groups were significantly higher but their serum Ca and P levels were significantly lower compared to the control group. CONCLUSION We think that serum sclerostin concentrations, which were significantly higher in patients with cCOM and ncCOM compared to healthy controls are associated with bone erosion. There is a need for further studies with larger samples in order to determine the relationship between sclerostin and bone erosion in cholesteatoma to help in establishing preventive measures against cholesteatoma and set new targets for the development of non-surgical treatments.

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SUMMARY OBJECTIVE Sclerostin is a glycoprotein that plays a catabolic role in bone and is involved in the regulation of bone metabolism by increasing the osteoclastic bone resorption. In this study, serum sclerostin levels were measured in chronic otitis media (COM) with and without cholesteatoma, assuming that it might have a role in the aetiopathogenesis of bone resorption. METHODS A total of 44 patients with cholesteatomatous COM (cCOM) (n = 22) and non-cholesteatomatous COM (ncCOM) (n = 22) were included in this study, and 26 healthy volunteers without any chronic ear disease problem(s) constituted the control group (n = 26). RESULTS No significant difference was not found in terms of serum iPTH, ALP, and vitamin D levels between ncCOM, cCOM, and the control groups. A significant difference was found in terms of serum sclerostin, Ca, and P levels between ncCOM, cCOM, and the control groups (p<0.05). Serum sclerostin levels in the study groups were significantly higher but their serum Ca and P levels were significantly lower compared to the control group. CONCLUSION We think that serum sclerostin concentrations, which were significantly higher in patients with cCOM and ncCOM compared to healthy controls are associated with bone erosion. There is a need for further studies with larger samples in order to determine the relationship between sclerostin and bone erosion in cholesteatoma to help in establishing preventive measures against cholesteatoma and set new targets for the development of non-surgical treatments.

RESUMO OBJETIVO A esclerostina é uma glicoproteína que desempenha um papel catabólico no osso e também envolve a regulação do metabolismo ósseo, aumentando a reabsorção óssea osteoclástica. Neste estudo, os níveis séricos de esclerostina foram medidos em otite média crônica (OMC) com e sem colesteatoma, e presumiu-se se que ela poderia ter um papel na etiopatogênese da reabsorção óssea. MÉTODOS Um total de 44 pacientes com otite média crônica colesteatomatosa (OMCc) (n=22), não colesteatomatosa (OMCnc)(n=22) foram incluídos neste estudo, e 26 voluntários saudáveis e sem doenças crônicas do ouvido constituíram o grupo de controle (n=26). RESULTADOS Não foi encontrada diferença significativa em termos de níveis séricos de iPTH, ALP e vitamina D entre OMCnc, OMCc e o grupo de controle. Foi encontrada uma diferença significativa em termos de níveis séricos de esclerostina, Ca e P entre OMCnc, OMCc e o grupo de controle (p<0,05). Os níveis séricos de esclerostina nos grupos de estudo foram significativamente mais altos, mas os níveis séricos de Ca e P foram significativamente mais baixos em comparação com o grupo de controle. CONCLUSÃO Acreditamos que as concentrações séricas de esclerostina, significativamente maiores em pacientes com OMCc e OMCnc em relação aos controles saudáveis, estão associadas à erosão óssea. Há necessidade de mais estudos com amostras maiores para determinar a relação entre esclerostina e erosão óssea no colesteatoma, já que essas pesquisas podem ajudar a estabelecer medidas preventivas contra o colesteatoma e novas metas para o desenvolvimento de tratamentos não cirúrgicos.

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Middle ear cholesteatomas are characterized by the presence of keratinized stratified squamous epithelium inside this cavity. It is considered to be more aggressive in childhood. In normal skin, the epidermal growth factor receptor (EGFR) is expressed in the cytoplasmic membrane of epithelial cells of the basal layer. In contrast, its expression in middle ear cholesteatoma extends to suprabasal layers. The objective of this study is to detect the presence of EGFR in cases of acquired cholesteatoma of the middle ear and correlate the expression of this receptor with patients' ages. In this cross-sectional study, cholesteatoma samples were collected from 50 patients (35 adults and 15 children) who underwent otological surgery, throughout 1 year of study. These samples were subjected to histological and immunohistochemical assays. Results were submitted to statistical analyses and main findings were: EGFR was present in the parabasal layers in 27 cases and EGFR expression was extended to all layers of the matrix in 17 cases. There were no statistically significant differences in what concerns age-related variances in EGFR expression. The intensity and location of EGFR expression in acquired cholesteatoma of the middle ear confirm the hyperproliferative capacity of keratinocytes.

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UNLABELLED: Acquired middle ear cholesteatoma is a disease which promotes bone erosion resulting in potentially serious complications. The tumor necrosis factor alpha (TNF-α) is present in cholesteatoma and it is related to bone erosion, as shown by different authors. To understand the aggressiveness characteristics of cholesteatoma is necessary, however, to better address the presence and distribution of their receptors. OBJECTIVE: To evaluate the expression of type 2 TNF-α receptor (TNF-R2) in fragments of cholesteatoma and correlate it to the degree of inflammation present. MATERIAL AND METHODS: observational cross-sectional study, which analyzed 33 fragments of cholesteatomas through histological analysis and immunohistochemistry (using as primary antibody to TNF-R2 LabVision® brand). The evaluation was performed by means of a qualitative and semi-quantitative agreement with the observed intensity. For statistical analysis we used the Fisher exact test and Spearman's correlation coefficient (considered statistically significant when p < 0. 05). RESULTS: The expression of TNF-R2 was present in all fragments, however a statistical analysis showed no correlation or association between inflammation and the expression of TNF-R2. CONCLUSIONS: TNF-R2 is present in cholesteatoma of the middle ear, however, its expression is not directly related to the degree of inflammation observed in patients with this disease.

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Acquired middle ear cholesteatoma is a disease which promotes bone erosion resulting in potentially serious complications. The tumor necrosis factor alpha (TNF-α) is present in cholesteatoma and it is related to bone erosion, as shown by different authors. To understand the aggressiveness characteristics of cholesteatoma is necessary, however, to better address the presence and distribution of their receptors. OBJECTIVE: To evaluate the expression of type 2 TNF-α receptor (TNF-R2) in fragments of cholesteatoma and correlate it to the degree of inflammation present. MATERIAL AND METHODS: observational cross-sectional study, which analyzed 33 fragments of cholesteatomas through histological analysis and immunohistochemistry (using as primary antibody to TNF-R2 LabVision® brand). The evaluation was performed by means of a qualitative and semi-quantitative agreement with the observed intensity. For statistical analysis we used the Fisher exact test and Spearman´s correlation coefficient (considered statistically significant when p < 0. 05). RESULTS: The expression of TNF-R2 was present in all fragments, however a statistical analysis showed no correlation or association between inflammation and the expression of TNF-R2. CONCLUSIONS: TNF-R2 is present in cholesteatoma of the middle ear, however, its expression is not directly related to the degree of inflammation observed in patients with this disease.

O colesteatoma adquirido da orelha média promove erosão óssea, ocasionando complicações potencialmente graves. O fator de necrose tumoral alfa (TNF-α) está presente no colesteatoma adquirido da orelha média e relaciona-se com a erosão óssea, como demonstraram diferentes autores. Para que se compreenda as características de agressividade do colesteatoma, é necessário que se estude a presença e a distribuição seus receptores. OBJETIVO: Avaliar a expressão do receptor tipo dois do TNF-α (TNF-R2) em fragmentos de colesteatoma e relacioná-lo com o grau de inflamação. MATERIAL E MÉTODOS: Estudo observacional do tipo transversal. Foram analisados 33 fragmentos de colesteatomas, submetidos à análise histológica e imunoistoquímica (utilizando o TNF-R2 da marca Labvision®). A avaliação foi realizada de forma qualitativa e semiquantitativa, de acordo com a intensidade observada. Para a análise estatística, foram utilizados o teste exato de Fischer e o coeficiente de correlação de Spearman (estatisticamente significativo quando p < 0,05). RESULTADOS: A expressão do TNF-R2 estava presente em todos os fragmentos, entretanto a estatística não evidenciou correlação, nem associação entre o processo inflamatório e a expressão do TNF-R2. CONCLUSÕES: O TNF-R2 está presente no colesteatoma adquirido da orelha média. Entretanto, a sua expressão não está relacionada ao grau de inflamação.

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UNLABELLED: Several studies involving immunohistochemical methods to assess external auditory canal epidermis have been performed with different objectives. With this method it is possible to assess the expression of various antigens such as cytokeratins, cytokines, and hyperproliferation markers among others. AIM: to revise, describe and analyze the knowledge generated by identifiable papers published on the worldwide literature about immunohistochemical hyperproliferation markers in normal external auditory canal epidermis. MATERIALS AND METHODS: systematic review of the papers published until 2009, in indexed international journals. RESULTS: Various antigens related to hyperproliferation were investigated by immunohistochemical methods among the included papers. The most studied ones were cytokeratin 16, Ki-67 and PCNA. CONCLUSIONS: most of the studies utilized external auditory canal epidermis as control sample to study external ear or middle ear cholesteatoma with immunohistochemical methods. There is a hyperproliferative antigen concentration, such as CK16, Ki-67 and PCNA, in the annulus tympanicus, adjacent meatus and tympanic regions, mainly in the lower areas.

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Vários estudos envolvendo métodos imunoistoquímicos para avaliação da epiderme do meato acústico externo já foram realizados com os mais diversos objetivos. Por estes métodos é possível avaliar a expressão de antígenos como as citoqueratinas, citocinas, marcadores de hiperproliferação, entre outros. OBJETIVO: Revisar, descrever e analisar a expressão dos marcadores imunoistoquímicos de hiperproliferação na epiderme do meato acústico externo normal. MATERIAIS E MÉTODOS: Revisão sistemática de artigos publicados até o ano de 2009 em periódicos internacionais indexados. RESULTADOS: Vários antígenos relacionados à hiperproliferação foram pesquisados por meio de métodos imunoistoquímicos dentre os artigos analisados. Os mais estudados foram a citoqueratina 16, o Ki-67 e o PCNA. CONCLUSÕES: A maioria dos trabalhos utilizou fragmentos de epiderme do meato acústico externo como amostra controle para estudo imunoistoquímico do colesteatoma da orelha média ou externa. Há uma concentração de marcadores de hiperproliferação como a CK16, o Ki-67 e o PCNA no anel fibrocartilagíneo e nas regiões adjacentes do meato acústico externo e da membrana timpânica.

Several studies involving immunohistochemical methods to assess external auditory canal epidermis have been performed with different objectives. With this method it is possible to assess the expression of various antigens such as cytokeratins, cytokines, and hyperproliferation markers among others. AIM: to revise, describe and analyze the knowledge generated by identifiable papers published on the worldwide literature about immunohistochemical hyperproliferation markers in normal external auditory canal epidermis. MATERIALS AND METHODS: systematic review of the papers published until 2009, in indexed international journals. RESULTS: Various antigens related to hyperproliferation were investigated by immunohistochemical methods among the included papers. The most studied ones were cytokeratin 16, Ki-67 and PCNA. CONCLUSIONS: most of the studies utilized external auditory canal epidermis as control sample to study external ear or middle ear cholesteatoma with immunohistochemical methods. There is a hyperproliferative antigen concentration, such as CK16, Ki-67 and PCNA, in the annulus tympanicus, adjacent meatus and tympanic regions, mainly in the lower areas.

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AIM: This study is to determine the MMP2s presence in cholesteatomas and whether complicating cholesteatomas show a higher immunohistochemical expression of matrix metalloproteinase 2. Cholesteatoma produces enzymes that cause bone erosion like matrix metalloproteinase 2 (MMP2). MATERIAL AND METHODS: We analyzed the expression of MMP2 in invasive (causing complications) compared to latent cholesteatomas (not causing complications). A cross-sectional study with nineteen slides and paraffin blocks of cholesteatomas derived from mastoidectomies were located and processed, including 8 invasive and 11 latent cholesteatomas. Immunohistochemical technique was empregated to MMP2. RESULTS: The results are expressed as 0, + (to low), ++ and +++(high) according to the quantity and color of the immunohistochemical staining of MMP2. Higher expression of MMP2 was observed in 7 (87.5%) of the 8 invasive cholesteatomas. With respect to latent cholesteatomas, higher expression of MMP2 was observed in 27.3% (3 cases), with Fishers exact test indicating a significant difference (p=0.015). CONCLUSIONS: Cholesteatoamas express MMP2 and Invasive cholesteatomas had high MMP2 compared to latent cholesteatomas.

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UNLABELLED: Cholesteatoma may cause bone erosion, with high morbidity and mortality rates. Tumor necrosis factor-alpha (TNF-a) is one of the main cytokines involved in this process. Our goal was to evaluate the role of TNF-a in Bone Resorption and its effect on cholesteatoma. MATERIAL AND METHODS: analysis and critical literature review. RESULTS: Different studies have demonstrated that TNF-a is capable of causing bone erosion. It may stimulate the differentiation and maturation of osteoclasts or it may act on the bone matrix, exposing it to the action of the osteoclasts. It is possible to inhibit TNF-a, reducing its effects and prevent bone loss in illnesses such as rheumatoid arthritis,and there has been no specific investigation regarding cholesteatomas. All studies agree on the importance of TNF-a in the bone resorption process present in cholesteatomas, and on the degree of destruction observed; however, there is no consensus as to its location. These differences are probably due to receptor site. CONCLUSION: TNF-a, present in cholesteatomas, promotes bone resorption, along with other cytokines (RANKL and IL-1) related to complications.

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Este estudo foi desenvolvido para determinar a presença de MMP2 em colesteatomas humanos e observar se colesteatomas que complicam (invasivos) apresentam uma maior expressão imunohistoquímica de Matriz Metaloproteinase 2 (MMP2). Colesteatomas produzem enzimas que causam erosão óssea, como a MMP2. MATERIAL E MÉTODO: Analisamos a expressão imunohistoquímica de MMP2 em colesteatomas invasivos, comparando-os aos latentes. Um estudo de corte transversal com dezenove lâminas e blocos parafinados de colesteatoma, derivados de mastoidectomias, foram desparafinados e submetidos à técnica imunohistoquímica com anticorpos anti-MMP2. RESULTADOS: Os resultados foram expressos em 0 (tênue), + (leve), ++ (moderado) e +++ (intenso), de acordo com a intensidade da expressão de MMP2. As expressões 0 e + foram denominadas Fraca e as expressões ++ e +++, Forte. Dos 8 colesteatomas invasivos, 7 apresentaram Forte expressão de MMP2 (87,5 por cento). Com relação aos colesteatomas latentes (11), apenas 3 apresentaram Forte expressão de MMP2 (27,3 por cento), com um teste exato de Fisher significante (p= 0,015). CONCLUSÃO: Colesteatomas expressam MMP2 e colesteatomas invasivos expressam MMP2 com maior intensidade, em relação aos latentes.

AIM: This study is to determine the MMP2Æs presence in cholesteatomas and whether complicating cholesteatomas show a higher immunohistochemical expression of matrix metalloproteinase 2. Cholesteatoma produces enzymesthat cause bone erosion like Matrixmetalloproteinase 2 (MMP2). MATERIAL AND METHODS: We analyzed the expression of MMP2 in invasive (causing complications) compared to latent cholesteatomas (not causing complications). A crosssectional study with nineteen slides and paraffin blocks of cholesteatomas derived from mastoidectomies were located and processed, including 8 invasive and 11 latent cholesteatomas. Immunohistochemical thecnique was empregated to MMP2. RESULTS: The results are expressed as 0, + (to low), ++ and +++(high) according to the quantity and color of the immunohistochemical staining of MMP2. Higher expression of MMP2 was observed in 7 (87.5 percent) of the 8 invasive cholesteatomas. With respect to latent cholesteatomas, higher expression of MMP2 was observed in 27.3 percent (3 cases), with FisherÆs exact test indicating a significant difference (p=0.015). CONCLUSIONS: Cholesteatoamas express MMP2 and Invasive cholesteatomas had high MMP2 compared to latent cholesteatomas.

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