Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity
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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.
Abstract
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.
참고문헌 (30)
- Olszewska E, "Etiopathogenesis of cholesteatoma", Eur Arch Otorhinolaryngol, 261(1), pp.6~24 (2004)
- Bujia J, "Hyperproliferation-associated keratin expression in human middle ear cholesteatoma", Acta Otolaryngol, 113(3), pp.364~368 (1993)
- Steven K. Juhn, "The Role of Inflammatory Mediators in the Pathogenesis of Otitis Media and Sequelae", Clinical and Experimental Otorhinolaryngology, 1(3), pp.117~138 (2008), 대한이비인후과학회
- Peek FA, "Lipopolysaccharide concentration and bone resorption in cholesteatoma", Otol Neurotol, 24(5), pp.709~713 (2003)
- Olszewska E, "Cholesteatoma-associated pathogenicity: potential role of lysosomal exoglycosidases", Otol Neurotol, 33(4), pp.596~603 (2012)
- Sikka K, "Evaluation of epithelial proliferation in paediatric and adult cholesteatomas using the Ki-67 proliferation marker", J Laryngol Otol, 126(5), pp.460~463 (2012)
- Mallet Y, "Aggressiveness and quantification of epithelial proliferation of middle ear cholesteatoma by MIB1", Laryngoscope, 113(2), pp.328~331 (2003)
- Banco B, "Canine aural cholesteatoma: a histological and immunohistochemical study", Vet J, 200(3), pp.440~445 (2014)
- Shiwa M, "Expression of transforming growth factor-alpha (TGF-alpha) in cholesteatoma", J Laryngol Otol, 112(8), pp.750~754 (1998)
- Yamamoto-Fukuda T, "Expression of keratinocyte growth factor and its receptor in noncholesteatomatous and cholesteatomatous chronic otitis media", Otol Neurotol, 31(5), pp.745~751 (2010)
- Macias MP, "Increased amphiregulin expression as a biomarker of cholesteatoma activity", Laryngoscope, 120(11), pp.2258~2263 (2010)
- Lee SH, "Telomerase activity and cell proliferation index in cholesteatoma", Acta Otolaryngol, 125(7), pp.707~712 (2005)
- Yetiser S, "Expression of epidermal growth factor, tumor necrosis factor-alpha, and interleukin-1alpha in chronic otitis media with or without cholesteatoma", Otol Neurotol, 23(5), pp.647~652 (2002)
- Juhasz A, "Elevated level of tenascin and matrix metalloproteinase 9 correlates with the bone destruction capacity of cholesteatomas", Otol Neurotol, 30(4), pp.559~565 (2009)
- Oger M, "The effect of BMP-2, BMP-4 and BMP-6 on bone destruction of cholesteatoma presence", Am J Otolaryngol, 34(6), pp.652~657 (2013)
- Kuo CL., "Etiopathogenesis of acquired cholesteatoma: prominent theories and recent advances in biomolecular research", Laryngoscope, 125(1), pp.234~240 (2015)
- Vennix PP, "Epidermal differentiation in the human external auditory meatus", Laryngoscope, 106(4), pp.470~475 (1996)
- Vennix PP, "Keratinocyte differentiation in acquired cholesteatoma and perforated tympanic membranes", Arch Otolaryngol Head Neck Surg, 122(8), pp.825~832 (1996)
- Sudhoff H, "Expression of a cell-cycle-associated nuclear antigen (MIB 1) in cholesteatoma and auditory meatal skin", Laryngoscope, 105(11), pp.1227~1231 (1995)
- Raynov AM, "Nucleoplasm staining patterns and cell cycle-associated expression of Ki-67 in middle ear cholesteatoma", Am J Otolaryngol, 26(5), pp.296~301 (2005)
- Akdogan V, "Role of Langerhans cells, Ki-67 protein and apoptosis in acquired cholesteatoma: prospective clinical study", J Laryngol Otol, 127(3), pp.252~259 (2013)
- Chung JH, "Expression of apoptotic vs antiapoptotic proteins in middle ear cholesteatoma", Otolaryngol Head Neck Surg, 153(6), pp.1024~1030 (2015)
- Kuczkowski J, "Expression patterns of Ki-67 and telomerase activity in middle ear cholesteatoma", Otol Neurotol, 28(2), pp.204~207 (2007)
- Aslier M, "Analysis of histopathological aspects and bone destruction characteristics in acquired middle ear cholesteatoma of pediatric and adult patients", Int J Pediatr Otorhinolaryngol, 82, pp.73~77 (2016)
- Kim HJ, "Increased proliferation and migration of epithelium in advancing experimental cholesteatomas", Otol Neurotol, 23(6), pp.840~844 (2002)
- Lee RJ, "The nature of the epithelium in acquired cholesteatoma: part 3: cytokeratin patterns in aural epithelial and cholesteatoma cells grown in cell culture", Clin Otolaryngol Allied Sci, 19(6), pp.516~520 (1994)
- Toyoshima T, "Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma", J Cancer Res Clin Oncol, 134(4), pp.515~521 (2008)
- Mikami T, "Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ", Oral Oncol, 47(6), pp.497~503 (2011)
- Jin L, "Keratin 17: a critical player in the pathogenesis of psoriasis", Med Res Rev, 34(2), pp.438~454 (2014)
- Desloge RB, "DNA analysis of human cholesteatomas", Am J Otol, 18(2), pp.155~159 (1997)