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Distribution of epithelial growth factor receptor in middle ear cholesteatoma (29 cases) Epithelium Strongly positive/positive Negative n (%) n (%)
Source publication
Middle ear cholesteatoma is destructive to auditory ossicles and temporal bone, and treatment usually includes surgical removal of all epithelial content in the tympanomastoid cavity. Epidermal growth factor receptor (EGFR) is a 170 kd to 180 kd transmembrane glycoprotein and its distribution density is related to the ability of the keratinocytes t...
Context in source publication
Similar publications
Chronic otitis media may be due to chronic mucosal disease or cholesteatoma. Differentiating the two is usually achieved by clinical examination. The computed tomography (CT) scan is the standard imaging technique for the temporal bone, but its exact role in the preoperative assessment of patients with chronic otitis media is controversial. In this...
High recurrence rate of the middle ear cholesteatoma requires regular postoperative follow-up. This study evaluated data from the patients investigated with DW MRI to ascertain (1) the strength of the technique in detecting primary, and residual recurrent cholesteatoma, and (2) its accuracy in differentiating cholesteatoma from postoperative tissue...
Purpose
The use of Balloon Eustachian tuboplasty (BET) for Eustachian tube dysfunction is increasing in adults but to a lesser extent in children. Despite growing experience, concerns remain that BET could theoretically cause carotid artery rupture, which may be more likely if there is carotid canal dehiscence adjacent to the bony Eustachian tube....
Objectives: To analyze the miRNAs expression profiling between acquired middle ear cholesteatoma and normal skin, and to identify several novel miRNAs which may be involved in the etiopathogenesis of middle ear cholesteatoma.
Methods: MiRNA microarray technology was adopted to analyze the miRNA expression profiling between acquired middle ear chole...
Citations
... Cholesteatoma of the middle ear is a disease characterized by the presence of keratinized squamous stratified epithelium inside this cavity, replacing the normal cover tissue: ciliated columnar pseudo-stratified epithelium in the peritubal region and simple squamous to columnar epithelium in the remainder of the middle ear [5,7,8,10,12,15,16]. Its insidious manifestation in the childhood may result from dysfunctions of the auditory tube, due to nasal and pharyngeal diseases, such as sinusitis, allergic rhinitis, velopharyngeal incompetence. ...
... Recently, several studies have described EGFR expression in cases of middle ear cholesteatoma [3,7,8,12,14,16,18]. ...
... Several authors have analyzed EGFR expression in cases of cholesteatoma [3,4,7,8,10,12,14,16,18]. Immunohis-tochemical methods have been used most frequently [3,7,8,12,14,16,18], and these are considered to be the gold standard for detecting this receptor. ...
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.
... The epidermal growth factor receptor (EGFR) is important for proliferation, diVerentiation, adhesion, migration und apoptosis of epithelial cells. EGFR was chosen as an additional extracellular marker because of its (over-)expression in many epithelial tumors [5,11,27]. The selectivity of these cellular targets was checked by comparison of cholesteatoma and middle ear mucosa cells. ...
Cholesteatoma is a destructive ear condition requiring complete surgical removal. One major problem lies in the frequent occurrence of residual cholesteatoma caused by squamous epithelium remaining in the middle ear. Our aim is to develop a laser treatment that is selectively directed against residual cholesteatoma cells and can be performed after cholesteatoma surgery in the same session. In a first trial, we studied the photodynamic effect of argon (AL) and diode lasers (DL) on cholesteatoma tissue. Intraoperatively harvested monolayer-cultured cholesteatoma cells were stained in vivo with different absorption enhancers: neutral red (NR), fluorescein diacetate (FDA), and indocyanine green (ICG). In vitro, staining tests on enhanced cellular dye absorption and laser tests were followed by cytotoxicity measurements to determine the respective amount of damage. To achieve selective cell destruction, antibody-mediated staining of cholesteatoma and middle ear mucosa cells was examined in a second trial. Cell cultures (cytospin and coverglass growing) and paraffin-embedded cholesteatoma tissue sections were studied immunohistochemically to determine the binding of monoclonal mouse antibodies against human cytokeratins CK5, CK10, CK14 and the epidermal growth factor receptor EGFR. Intracellular staining with absorption enhancers increased the optical density at the wavelength corresponding to the dye. Staining and subsequent laser irradiation destroyed up to 92% of cultured cholesteatoma cells. Unstained irradiated tissue was not affected. In cytospins, the antibody against CK5/6 showed strong staining of cholesteatoma and weak staining of mucosa cells. Reactivity for CK14 and EGFR was positive in both tissues. In coverglass cultures, staining of cholesteatoma cells was positive for CK5/6, CK14 and EGFR. Mucosa cells were positive for EGFR but negative for cytokeratins. Both cell types were negative for CK10. In embedded cholesteatoma tissue, CK5/6 and CK14 were localized in the basal layers of the matrix, while CK10 was situated in the suprabasal layers, and EGFR was present in all layers of the matrix and perimatrix. As for the technical aspects of laser-assisted cholesteatoma surgery, AL and DL have proved to be suitable devices; ICG and FDA are effective nontoxic absorption enhancers. The investigated antibodies against cytokeratins and EGFR show nonselective staining and thus appear to be inappropriate for avoiding unwanted cell damage. For safe and specific intraoperative application to intact tissue, the chromophore should be coupled to a particular antibody that binds solely to an easily accessible specific antigen at the surface of cholesteatoma cells.
Objectives/Hypothesis
The pathophysiology of cholesteatoma is not precisely understood, and research on the associated microRNAs (miRNAs) is also deficient. We demonstrated the expression of miRNA in normal skin and middle ear cholesteatoma by next‐generation sequencing (NGS) technology. The profiles of miRNA and relevant molecular interaction pathways were investigated.
Study Design
Case–control experimental study.
Methods
Middle ear cholesteatoma and post‐auricular skin tissue specimens were collected from 13 adult patients. Total RNA was extracted, and miRNA expression profiles were analyzed by NGS technology. Functional gene classification to predict target genes and relevant biological pathways was performed using DIANA‐microT‐CDS and the Kyoto Encyclopedia Gene and Genome database (KEGG) pathways.
Results
The expression of 2588 miRNAs from middle ear cholesteatoma and skin tissue samples was analyzed. The expression of 76 upregulated and 128 downregulated miRNAs was identified in the cholesteatoma samples compared to normal skin (FC ≥2 and p < 0.05). Ninety‐nine differentially expressed miRNAs (FC ≥4 and p < 0.05) were used to explore the biological pathways involved in the etiopathogenesis of cholesteatoma. The most predicted pathway in cholesteatoma in the upregulated miRNA group was the ErbB signaling pathway and it was extracellular matrix (ECM)–receptor interaction in the downregulated miRNA group.
Conclusions
This was the first study investigating small miRNAs in human acquired cholesteatoma using NGS technique. We were able to identify new miRNAs and pathways related to cholesteatoma. The results of this study are expected to be helpful in revealing new pathophysiologies of cholesteatoma.
Level of Evidence
N/A Laryngoscope , 2024
Conclusion:
The detection of the HER4 receptor in 50% of cholesteatomas but never in the reference tissue, and the increased expression of its activating ligand EPI, suggest that EPI-mediated activation of HER4 might play a role in cholesteatoma growth.
Objective:
To investigate the expression of the epidermal growth factor (EGF) system in human middle ear cholesteatoma.
Methods:
Forty-seven patients referred for surgery due to cholesteatoma were included in the study. Clinical data were collected. Biopsies of cholesteatoma and skin from the external ear canal were obtained during surgery. mRNA expression was quantified with real-time PCR. The corresponding proteins were visualized using immunohistochemistry.
Results:
A systematic investigation of all four receptors, HER1, HER2, HER3, and HER4, and the ligands EGF, transforming growth factor (TGF)-α, amphiregulin (AR), heparin-binding EGF-like growth factor (HB-EGF), and epiregulin (EPI) of the EGF system is presented. At the mRNA level, the study demonstrates an up-regulation of mRNA encoding EPI and AR. In contrast HER1 and EGF were down-regulated. HER4 mRNA could be detected in 50% of cholesteatoma and 20% of reference tissues, and the HER4 protein was detectable only in cholesteatoma tissue. HER1 and HER2 were also visualized by immunohistochemistry, whereas the ligands EPI, AR, and EGF were undetectable with our methods.
