Keratinocyte Differentiation in Acquired Cholesteatoma and Perforated Tympanic Membranes

Vennix, P.P.C.A.; Kuijpers, W.; Peters, Theo; Tonnaer, E.L.G.M.; Ramaekers, Frans C. S.

doi:10.1001/archotol.1996.01890200015003

Cited by 20 publications

(17 citation statements)

References 28 publications

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“…The present observations demonstrate that the expression of Ck 17 is similar to that of the hyperproliferation-associated marker Ck 16. This observation supports the assumption of de Jong et al [22] and Vennix et al [23] that Ck 17 might be associated with hyperproliferation.…”

Section: Discussionsupporting

confidence: 90%

Expression of Cytokeratin Subtypes and Vimentin in Squamous Cell Carcinoma of the Floor of the Mouth and the Mobile Tongue

Velden

Schaafsma

Manni

et al. 2001

Otorhinolaryngol Nova

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Objectives: The assessment of the expression patterns of cytokeratin polypeptides (Cks) and vimentin in normal epithelium of the mobile tongue and floor of the mouth, squamous cell carcinomas and their lymph node metastases. Material and Methods: Chain-specific monoclonal antibodies to various Cks and vimentin were used, employing the immunoperoxidase technique. Results and Conclusions: Profound changes in the expression of pre-existing Cks and de novo expression of simple epithelium-related Cks and of vimentin occurred upon malignant transformation and tumor progression. Changes were mainly related to the degree of cellular differentiation, tumor cell morphology and tumor growth pattern. Low-grade tumors showed a pronounced decrease of the stratification Cks 4 and 13, and an increase of Cks 14, 16, and 17. With increasing tumor grade, expression of Cks 16 and 17 decreased. De novo expression of Cks 8 and 18 and of vimentin was most marked in high-grade tumors, in tumors with a basaloid phenotype and in tumors growing in small infiltrating tumor fields; it was proposed to be associated with poor prognosis.

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Section: Discussionsupporting

confidence: 90%

Expression of Cytokeratin Subtypes and Vimentin in Squamous Cell Carcinoma of the Floor of the Mouth and the Mobile Tongue

Velden

Schaafsma

Manni

et al. 2001

Otorhinolaryngol Nova

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“…Não houve correlação entre esses dois grupos e a presença das variáveis CK 16 e Ki-67 suprabasal ou apical. Portanto, neste estudo, pode-se inferir que a inflamação seja uma variável encontrada em praticamente todos os casos de colesteatoma, mas não foi observada correlação positiva entre a intensidade da inflamação e a presença da CK 16 ou do Ki-67 suprabasal e apical, diferentemente dos achados de Sudhoff et al 23 , Sudhoff et al 22 e Vennix et al 24 . Continuando a análise estatística das variáveis estudadas, procurou-se verificar alguma relação entre a existên-cia de complicações e a presença das variáveis Ki-67 suprabasal, Ki-67 apical, CK 16, hiperplasia da camada basal com cones epiteliais e inflamação (moderada e acentuada).…”

Section: Discussionunclassified

Imunoexpressão da citoqueratina 16 e do antígeno nuclear Ki-67 no colesteatoma adquirido da orelha média

Pereira¹,

Almeida

Vianna

2002

Rev. Bras. Otorrinolaringol.

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Introdução: Ocolesteatoma da orelha média é caracterizado pela presença de epitélio escamoso estratificado queratinizado nesta cavidade, causando destruição óssea e podendo levar a complicações. Algumas substâncias como a citoqueratina 16 e o Ki-67, marcadores de proliferação celular, vêm sendo utilizadas para estudar essa doença. A CK 16 é um filamento protéico, situado no citoplasma das células epiteliais, característico de epitélios hiperproliferativos. O Ki-67 é um antígeno nuclear que aparece nas células em está-gio de proliferação. Objetivo: O objetivo deste trabalho foi estudar a imunoexpressão da CK 16 e do Ki-67 no colesteatoma adquirido. Forma de estudo: Clínico prospectivo. Material e Método: Foram colhidas amostras de colesteatoma de 31 pacientes submetidos à cirurgia otológica, sendo 20 adultos e 11 crianças, no período de 1998 e 2000. Essas amostras foram submetidas à análise histológica e imunohistoquímica para estudo da expressão da CK 16 e do Ki-67 na matriz do colesteatoma. Resultado: A análise dos resultados mostrou a presença da CK 16 nas camadas suprabasais da matriz do colesteatoma e, do Ki-67, na camada basal, estendendo-se para as camadas suprabasais e, inclusive, para a camada apical da matriz. A reação aos anticorpos anti-CK 16 e Ki-67 foi heterogênea. A correlação entre a CK 16 e o Ki-67 suprabasal com variáveis morfológicas, como acantose do epitélio e hiperplasia da camada basal formando cones epiteliais em direção à perimatriz, foi positiva e significativa. Também houve relação positiva e significativa entre a CK 16 e o Ki-67 suprabasal e apical. Conclusão: Esses resultados permitem concluir que o colesteatoma tem características hiperproliferativas, expressando a CK 16 e o Ki-67 na sua matriz.

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“…Although different studies have shown the invasive and hyperproliferative behaviour of the CHO epidermal tissue (Bujia et al 1993; Vennix et al 1996), very little is still known about the molecular mechanisms involved in the pathogenesis of the disease. Others and we have suggested that the proliferation and migration of the keratinocytes in CHO might be mediated by an altered release of autocrine and paracrine growth factors and a modulated expression of their receptors (Kojima et al 1994; Tanaka et al 1999; Yetiser et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Cholesteatoma-associated fibroblasts modulate epithelial growth and differentiation through KGF/FGF7 secretion

Raffa

Leone

Scrofani

et al. 2012

Histochem Cell Biol

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The keratinocyte growth factor (KGF/FGF7), produced by stromal cells, is a key paracrine mediator of epithelial proliferation, differentiation and migration. Expression of the growth factor is increased in wound healing and in hyperproliferative epithelial diseases, as a consequence of the activation of dermal fibroblasts by the inflammatory microenvironment. The middle ear cholesteatoma, an aural epidermal pathology characterized by keratinocyte hyperproliferation and chronic inflammation, may represent a model condition to study the epithelial-mesenchymal interactions. To develop an in vitro model for this disease, we isolated and characterized human primary cultures of fibroblasts associated with the cholesteatoma lesion, analyzing their secretory behaviour and degree of differentiation or activation. Compared to the perilesional or control normal fibroblasts, all cultures derived from cholesteatoma tissues were less proliferating and more differentiated and their highly variable activated phenotype correlated with the secretion of KGF as well as of metalloproteases 2 and 9. Culture supernatants collected from the cholesteatoma-associated fibroblasts were able to increase the proliferation and differentiation of human keratinocytes assessed by the expression of Ki67 and keratin-1 markers. The single crucial contribution of the KGF released by fibroblasts on the keratinocyte biological response was shown by the specific, although partial, block induced by inhibiting the KGF receptor or by immunoneutralizing the growth factor. Altogether, these results suggest that the activation of the stromal fibroblasts present in the pathological tissue, and the consequent increased secretion of KGF, play a crucial role in the deregulation of the epidermal proliferation and differentiation.

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Keratinocyte Differentiation in Acquired Cholesteatoma and Perforated Tympanic Membranes

Cited by 20 publications

References 28 publications

Expression of Cytokeratin Subtypes and Vimentin in Squamous Cell Carcinoma of the Floor of the Mouth and the Mobile Tongue

Expression of Cytokeratin Subtypes and Vimentin in Squamous Cell Carcinoma of the Floor of the Mouth and the Mobile Tongue

Imunoexpressão da citoqueratina 16 e do antígeno nuclear Ki-67 no colesteatoma adquirido da orelha média

Cholesteatoma-associated fibroblasts modulate epithelial growth and differentiation through KGF/FGF7 secretion

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