Role of Langerhans cells, Ki-67 protein and apoptosis in acquired cholesteatoma: prospective clinical study

Akdogan, Volkan; Yılmaz, İsmail; Canpolat, Tuba; Özlüoğlu, Levent N.

doi:10.1017/s0022215112003180

Cited by 10 publications

(7 citation statements)

References 15 publications

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“…Nevertheless, we see that there is an indigence to conduct universally approved guidelines to objectively measure cholesteatoma aggressiveness. We confirmed that cholesteatoma expressed higher Ki-67 levels than the meatal skin (the mean ratio was nearly doubled in cholesteatoma, P <0.001), and the results were compatible with the previous studies [ 19 - 21 ]. Additionally, both higher labeling in the invasive group and moderately positive correlation with the grading score of bone erosion ( Table 2 ) suggest an important role of Ki-67 in bone destruction ( P =0.029, P =0.015, respectively).…”

Section: Discussionsupporting

confidence: 92%

Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity

Hamed

Nakata

Shiogama

et al. 2017

Clin Exp Otorhinolaryngol

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Objectives Cholesteatoma is a nonneoplastic destructive lesion of the temporal bone with debated pathogenesis and bone resorptive mechanism. Both molecular and cellular events chiefly master its activity. Continued research is necessary to clarify factors related to its aggressiveness. We aimed to investigate the expression of Ki-67, cytokeratin 13 (CK13) and cytokeratin 17 (CK17) in acquired nonrecurrent human cholesteatoma and correlate them with its bone destructive capacity.Methods A prospective quantitative immunohistochemical study was carried out using fresh acquired cholesteatoma tissues (n=19), collected during cholesteatoma surgery. Deep meatal skin tissues from the same patients were used as control (n=8). Cholesteatoma patients were divided into 2 groups and compared (invasive and noninvasive) according to a grading score for bone resorption based upon clinical, radiologic and intraoperative findings. To our knowledge, the role of CK17 in cholesteatoma aggressiveness was first investigated in this paper.Results Both Ki-67 and CK17 were significantly overexpressed in cholesteatoma than control tissues (P<0.001 for both Ki-67 and CK17). In addition, Ki-67 and CK17 were significantly higher in the invasive group than noninvasive group of cholesteatoma (P=0.029, P=0.033, respectively). Furthermore, Ki-67 and CK17 showed a moderate positive correlation with bone erosion scores (r=0.547, P=0.015 and r=0.588, P=0.008, respectively). In terms of CK13, no significant difference was found between cholesteatoma and skin (P=0.766).Conclusion Both Ki-67 and CK17 were overexpressed in cholesteatoma tissue and positively correlated with bone resorption activity. The concept that Ki-67 can be a predictor for aggressiveness of cholesteatoma was supported. In addition, this is the first study demonstrating CK17 as a favoring marker in the aggressiveness of acquired cholesteatoma.

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Section: Discussionsupporting

confidence: 92%

Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity

Hamed

Nakata

Shiogama

et al. 2017

Clin Exp Otorhinolaryngol

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“…Our previous work in this regard had also demonstrated a significantly increased expression of Ki67 in cholesteatoma specimens when compared to controls [ 8 ]. Almost all previous studies have reported similar findings [ 9 – 13 ].…”

Section: Discussionsupporting

confidence: 77%

Immunohistochemical Analysis of the Expression of Cytokeratins in Acquired Cholesteatoma and Its Clinico-Radiological Correlation

et al. 2023

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Background and Objectives: Cholesteatomatous chronic otitis media acquires epithelial proliferation and differentiation characteristics, which render it able to erode the underlying bone and cause complications. We attempt to characterize the cholesteatoma epithelium by observing the expression of cytokeratins (such as 34ße12, CK17, and CK13) and Ki67 among patients with cholesteatoma with different aggressiveness as compared to disease-free controls. Subjects and Methods: In this prospective study (2017)(2018)(2019)(2020)(2021), we enrolled all consenting consecutive patients with cholesteatomatous chronic otitis media. They were staged in accordance with the staging guidelines of the European Academy of Otology and Neurotology and the Japanese Otological Society. Bony external auditory canal (EAC) skin specimens of the patients undergoing tympanoplasty were chosen as controls. We did an immunohistochemical analysis of the cholesteatoma specimens and normal bony EAC controls by observing the expression of 34ße12, CK17, CK13, and Ki67 across the layers of the epithelium. Fisher's exact test and chi-square test were used to evaluate any statistical significance between the cases and the controls, and the subgroups were made based on the clinical stage. Results: An increased expression of CK17 (p<0.001), CK13 (p<0.03), and Ki67 (p<0.001) was observed in cholesteatoma specimens when compared to normal bony EAC controls. Also, there was a loss of expression of 34ße12 in a subset of cholesteatoma specimens, all of which showed full-thickness expression of CK13. There was no difference in the expression of cytokeratin among specimens from patients belonging to different subgroups based on clinical stage, age, sex, duration of ear symptoms, or type of hearing loss (conductive vs. sensorineural). Conclusions: The majority of cholesteatoma specimens significantly overexpressed CK17, CK13, and Ki67 when compared to normal bony EAC skin controls, while a subset showed loss of expression of 34ße12, which provides some insight into its pathogenesis.

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“…To prove the hyperproliferative activity of cholesteatoma cells compared to the control skin cells, we used Ki-67 and NF-κβ. Several authors presented the upregulation of Ki-67 in cholesteatoma [ 30 , 31 , 32 ]. Our results were similar and showed a statistically significant overexpression of Ki-67 in the matrix ( p = 0.000) and perimatrix ( p = 0.010) compared to the epithelium and connective tissue of the skin.…”

Section: Discussionmentioning

confidence: 99%

Morphopathogenesis of Adult Acquired Cholesteatoma

2023

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Background and Objectives. The aim of this study was to compare the distribution of proliferation markers (Ki-67, NF-κβ), tissue-remodeling factors (MMP-2, MMP-9, TIMP-2, TIMP-4), vascular endothelial growth factor (VEGF), interleukins (IL-1 and IL-10), human beta defensins (HβD-2 and HβD-4) and Sonic hedgehog gene protein in cholesteatoma and control skin. Methods. Nineteen patient cholesteatoma tissues and seven control skin materials from cadavers were included in the study and stained immunohistochemically. Results. Statistically discernible differences were found between the following: the Ki-67 in the matrix and the Ki-67 in the skin epithelium (p = 0.000); the Ki-67 in the perimatrix and the Ki-67 in the connective tissue (p = 0.010); the NF-κβ in the cholesteatoma matrix and the NF-κβ in the epithelium (p = 0.001); the MMP-9 in the matrix and the MMP-9 in the epithelium (p = 0.008); the HβD-2 in the perimatrix and the HβD-2 in the connective tissue (p = 0.004); and the Shh in the cholesteatoma’s perimatrix and the Shh in the skin’s connective tissue (p = 0.000). Conclusion. The elevation of Ki-67 and NF-κβ suggests the induction of cellular proliferation in the cholesteatoma. Intercorrelations between VEGF, NF-κβ and TIMP-2 induce neo-angiogenesis in adult cholesteatoma. The similarity in the expression of IL-1 and IL-10 suggests the dysregulation of the local immune status in cholesteatoma. The overexpression of the Sonic hedgehog gene protein in the cholesteatoma proves the selective local stimulation of perimatrix development.

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Role of Langerhans cells, Ki-67 protein and apoptosis in acquired cholesteatoma: prospective clinical study

Abstract: Using cell proliferation and apoptosis markers, a dense Langerhans cell infiltration was found to occur as a host response to middle-ear cholesteatoma.

Cited by 10 publications

References 15 publications

Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity

Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity

Immunohistochemical Analysis of the Expression of Cytokeratins in Acquired Cholesteatoma and Its Clinico-Radiological Correlation

Morphopathogenesis of Adult Acquired Cholesteatoma

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