Immunohistochemical Analysis of the Expression of Cytokeratins in Acquired Cholesteatoma and Its Clinico-Radiological Correlation
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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 (2017-2021), 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 (<i>p</i><0.001), CK13 (<i>p</i><0.03), and Ki67 (<i>p</i><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.
Abstract
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 (2017-2021), 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 (<i>p</i><0.001), CK13 (<i>p</i><0.03), and Ki67 (<i>p</i><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.
참고문헌 (17)
- "ICMR Multicentric National Task Force Project “Prevalence and Etiology of Hearing Impairment” Manual for Capacity Building and Monitoring" (2020)[URL]
- Schweizer J, "New consensus nomenclature for mammalian keratins", J Cell Biol, 174, pp.169~174 (2006)
- Olszewska E, "Comparative cytokeratin distribution patterns in cholesteatoma epithelium", Histol Histopathol, 22, pp.37~42 (2007)
- Jin L, "Keratin 17 : a critical player in the pathogenesis of psoriasis", Med Res Rev, 34, pp.438~454 (2014)
- Sasaki H, "Expression of cytokeratins 13 and 16 in middle ear cholesteatoma", Otolaryngol Head Neck Surg, 110, pp.310~317 (1994)
- Mahmood A. Hamed, "Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity", Clinical and Experimental Otorhinolaryngology, 10(3), pp.213~220 (2017), 대한이비인후과학회[DOI]
- Yung M, "EAONO", JOS joint consensus statements on the definitions, classification and staging of middle ear cholesteatoma, 2017, pp.13, 1~8
- Sikka K, "Evaluation of epithelial proliferation in paediatric and adult cholesteatomas using the Ki-67 proliferation marker", J Laryngol Otol, 126, pp.460~463 (2012)
- Huisman MA, "Cholesteatoma epithelium is characterized by increased expression of Ki-67, p53 and p21, with minimal apoptosis", Acta Otolaryngol, 123, pp.377~382 (2003)
- Araz Server E, "Predictive role of Ki-67 and proliferative-cell nuclear antigen(PCNA)in recurrent cholesteatoma", J Int Adv Otol, 15, pp.38~42 (2019)
- Lasminingrum L, "Association of Ki-67 level on bone destruction in chronic suppurative otitis media patients with cholesteatoma", Syst Rev Pharm, 12, pp.644~649 (2021)
- Sanli A, "Evaluation of Ki-67 expression in recurrent cases of cholesteatoma", Kulak Burun Bogaz Ihtis Derg, 17, pp.65~69 (2007)
- Akdogan V, "Role of Langerhans cells, Ki-67 protein and apoptosis in acquired cholesteatoma : prospective clinical study", J Laryngol Otol, 127, pp.252~259 (2013)
- Sadé J, "The metaplastic and congenital origin of cholesteatoma", Acta Otolaryngol, 96, pp.119~129 (1983)
- Wittmaack K, "Wie entsteht ein genuines cholesteatom? Archiv für Ohren-", Nasen- und Kehlkopfheilkunde, 137, pp.306~332 (1933)
- Jackler RK, "A new theory on the pathogenesis of acquired cholesteatoma : mucosal traction", Laryngoscope, 125(Suppl 4), pp.S1~S14 (2015)
- Juhász A, "Elevated level of tenascin and matrix metalloproteinase 9 correlates with the bone destruction capacity of cholesteatomas", Otol Neurotol, 30, pp.559~565 (2009)