Naim Ramin, Riedel Frank, Hormann Karl
Department of Otolaryngology, Head and Neck Surgery, University of Mannheim, Germany.
Int J Mol Med. 2003 May;11(5):555-8.
External ear canal cholesteatoma (EACC) is an invasive and destructive chronic inflammation based on the uncontrolled proliferation of the keratinocytes with an osteolytic character predominantly present in the inferior part of the auditory canal. EACC is a rare otologic entity and the incidence is estimated about 1 patient per 1000 new otologic patients. Although, EACC was described already in 1850, the cause is still unknown. Poor blood supply resulting in hypoxia is assumed to be the major etiologic factor for establishing EACC. VEGF is known to be one of the most important regulators of angiogenesis predominantly released in hypoxic conditions. VEGF is thought to play an important role in many regulatory pathways besides angiogenesis. In order to reveal the role of VEGF in the pathogenesis of EACC we determined the difference of the VEGF-expression in EACC and normal auditory meatal skin (AMS). EACC samples showed an increased expression of VEGF in all layers of the EACC-epithelium whereas AMS was predominantly reactive in the basal layers. The underlying stroma exhibited different stain-intensity which was correlating to the density of inflammatory cells. In summary poor blood supply results in hypoxic conditions which supports epithelial migratory disturbances of the auditory meatal duct. In order to improve hypoxia VEGF is released to induce angiogenesis. One of the results is migration of the keratinocytes proliferating into adjacent tissue. This study revealed an increased expression of VEGF in all layers of the EACC-epithelium. Therefore it is considered that up-regulation of VEGF enables and supports the pathogenesis of EACC, and VEGF seems to be a pivotal factor for the manifestation of EACC. This is the first study describing VEGF expression in EACC and its difference to AMS.
外耳道胆脂瘤(EACC)是一种侵袭性和破坏性的慢性炎症,其基于角质形成细胞的不受控制的增殖,具有溶骨性特征,主要存在于耳道下部。EACC是一种罕见的耳科疾病,估计发病率约为每1000名新耳科患者中有1例。尽管EACC早在1850年就已被描述,但病因仍然不明。导致缺氧的血液供应不足被认为是EACC形成的主要病因。已知血管内皮生长因子(VEGF)是血管生成的最重要调节因子之一,主要在缺氧条件下释放。VEGF被认为除了血管生成外,在许多调节途径中也发挥着重要作用。为了揭示VEGF在EACC发病机制中的作用,我们测定了EACC和正常耳道皮肤(AMS)中VEGF表达的差异。EACC样本显示EACC上皮各层中VEGF表达增加,而AMS主要在基底层有反应。下层基质表现出不同的染色强度,这与炎症细胞的密度相关。总之,血液供应不足导致缺氧状态,这支持了耳道导管上皮迁移紊乱。为了改善缺氧,VEGF被释放以诱导血管生成。结果之一是角质形成细胞增殖迁移到相邻组织。本研究揭示了EACC上皮各层中VEGF表达增加。因此,认为VEGF的上调促成并支持了EACC的发病机制,并且VEGF似乎是EACC表现的关键因素。这是第一项描述EACC中VEGF表达及其与AMS差异的研究。