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Acquired cholesteatoma: summary of the cascade of molecular events

Published online by Cambridge University Press:  09 May 2013

L Louw
L Louw*
Affiliation:
Department of Otorhinolaryngology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
*
Address for correspondence: Dr L Louw, Department of Otorhinolaryngology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa E-mail: gnanll.md@ufs.ac.za
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Abstract

Background:

Cholesteatoma is considered a benign, gradually expanding and destructive epithelial lesion of the temporal bone. The pathogenesis of different classifications of cholesteatoma is marked by similar underlying cellular and molecular processes. Stepwise explanations of the histopathogenesis have been described previously. The current paper focuses on expounding the molecular events of cholesteatoma.

Method and results:

Cholesteatoma pathogenesis encompasses a complex network of signalling pathways during: epidermal hyperplasia, perimatrix–matrix interactions and mucosal disease. This paper presents a review of the molecular events driven by inflammatory mediators and enzymes during: cholesteatoma growth (cell proliferation and apoptosis); maintenance and deterioration (angiogenesis and hypoxia, oxidative stress and toxicity); and complications (bone erosion and hearing loss). The cascade of molecular events applicable to atelectasis and cholesteatoma that coexist with chronic otitis media and bone erosion as sequelae is summarised.

Conclusion:

The role of lipids in this disease is relatively unexplored, but there is evidence in support of fatty acid role-players that needs confirmation. Future directions in lipid research to delineate molecular mechanisms are proposed.

Keywords

CholesteatomaEarMiddleInflammationBiochemistryEnzymesPathology
Type
Review Articles
Information
The Journal of Laryngology & Otology , Volume 127 , Issue 6 , June 2013 , pp. 542 - 549
Copyright
Copyright © JLO (1984) Limited 2013 

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References

1Louw, L. Acquired cholesteatoma pathogenesis: stepwise explanations. J Laryngol Otol 2010;124:587–93CrossRefGoogle ScholarPubMed
2Olszewska, E, Wagner, M, Bernal-Sprekelson, M, Ebmeyer, J, Dazert, S, Hildmann, H et al. Etiopathogenesis of cholesteatoma. Eur Arch Otorhinolaryngol 2004;261:6–24CrossRefGoogle ScholarPubMed
3Tos, M. Manual of Middle Ear Surgery. New York: Thieme, 1993Google Scholar
4Seibert, JW, Danner, CJ. Eustachian tube function and the middle ear. Otolaryngol Clin North Am 2006;39:1221–35CrossRefGoogle ScholarPubMed
5Chole, RA, Sudhoff, HH. Chronic otitis media, mastoiditis and petrositis. In Cummings, Otolaryngology: Head and Neck Surgery, 4th edn: Mosby Elsevier, 2005;4:2988–3003Google Scholar
6Sudhoff, H, Tos, M. Pathogenesis of sinus cholesteatoma. Eur Arch Otorhinolaryngol 2007;264:137–43CrossRefGoogle ScholarPubMed
7Mishiro, Y, Sakagami, M, Kitahara, T, Kondoh, K, Okumura, S. The investigation of the recurrence rate of cholesteatoma using Kaplein-Meier survival analysis. Otol Neurotol 2008;29:803–6CrossRefGoogle ScholarPubMed
8Mustafa, A, Heta, A, Kastrai, B, Dreshaj, SH. Complications of chronic otitis media with cholesteatoma during a 10-year period in Kosovo. Eur Arch Otorhinolaryngol 2008;265:1477–82CrossRefGoogle ScholarPubMed
9Chole, RA, Faddis, BT. Evidence for microbial biofilms in cholesteatomas. Arch Otolaryngol Head Neck Surg 2002;128:1129–33CrossRefGoogle ScholarPubMed
10Post, JC, Hiller, NL, Nistico, L, Stoodley, P, Ehrlich, GD. The role of biofilms in otolaryngologic infections: update 2007. Curr Opin Otolaryngol Head Neck Surg 2007;15:347–51CrossRefGoogle ScholarPubMed
11Macassey, E, Dawes, P. Biofilms and their role in otorhinolaryngological disease. J Laryngol Otol 2008;122:1273–8CrossRefGoogle ScholarPubMed
12Wang, E, Jung, J, Nason, R, Pashia, M, Chole, R. Characterization of otopathogenic Pseudomonas aeruginosa: a biofilm phenotype. Arch Otolaryngol Head Neck Surg 2005;131:983–9CrossRefGoogle Scholar
13Junh, SK, Jung, M-K, Hoffman, MD, Drew, BR, Preciado, DA, Sausen, NJ et al. The role of inflammatory mediators in the pathogenesis of otitis media and sequelae. Clin Exp Otorhinolaryngol 2008;1:117–38Google Scholar
14Peek, FAW, Huisman, M, Berckmans, RJ, Sturk, A, van Loon, J, Grote, JJ. Lipopolysaccharide concentration and bone resorption in cholesteatoma. Otol Neurotol 2003;24:709–13CrossRefGoogle ScholarPubMed
15Dornelles, C, da Costa, SS, Meurer, L, Schweiger, C. Correlation of cholesteatomas perimatrix thickness with patient's age. Rev Bras J Otorrinolaringol 2005;6:792–7CrossRefGoogle Scholar
16Nagai, T, Suganuma, T, Ide, S, Shimoda, H, Kato, S. Confirmation of mucin in lymphatic vessels of acquired cholesteatoma. Eur Arch Otorhinolaryngol 2006;263:361–4CrossRefGoogle ScholarPubMed
17Sudhoff, H, Dazert, S, Gonzales, AM, Borkowski, G, Park, SY, Baird, A et al. Angiogenesis and angiogenic growth factors in middle ear cholesteatoma. Am J Otol 2000;21:793–8Google ScholarPubMed
18Adunka, O, Gstoettner, W, Knecht, R, Kiener, AC. Expression of hypoxia inducible factor 1 alpha and Von Hippel Lindau protein in human middle ear cholesteatoma. Laryngoscope 2003;113:1210–15CrossRefGoogle Scholar
19Olszewska, E, Chodynicki, S, Chyczewski, L. Apoptosis in the pathogenesis of cholesteatoma in adults. Eur Arch Otorhinolaryngol 2006;263:409–13CrossRefGoogle ScholarPubMed
20Alves, AL, Pereira, CSB, Carvalho M de, FP, Fregnani, JHTG, Ribeiro, FQ. EGFR expression in acquired middle ear cholesteatoma in children and adults. Eur J Pediatr 2012;171:307–10CrossRefGoogle ScholarPubMed
21Barbara, M, Raffa, S, Mure, C, Manni, V, Ronchetti, F, Monini, S et al. Keratinocyte growth factor receptor (KGF-R) in cholesteatoma tissue. Acta Otolaryngol 2008;128:360–4CrossRefGoogle ScholarPubMed
22Yamamoto-Fukuda, T, Takahasi, H, Koji, T. Expression of keratinocyte growth factor and its receptor in a middle ear cavity problem. Int J Pediatr Otorhinolaryngol 2012;76:76–81CrossRefGoogle Scholar
23Jin, BJ, Min, HJ, Jeong, JH, Park, CW, Lee, SH. Expression of EGFR and microvessel density in middle ear cholesteatoma. Clin Exp Otorhinolaryngol 2011;4:67–71CrossRefGoogle ScholarPubMed
24Macias, MP, Gerkin, RD, Macias, JD. Increased amphiregulin expression as a biomarker of cholesteatoma activity. Laryngoscope 2010;120:2258–63CrossRefGoogle ScholarPubMed
25Kucczkowski, J, Pawelczyk, T, Bakowska, A, Narozny, W, Mikaszewski, B. Expression of patterns of Ki-67 and telomerase activity in middle ear cholesteatoma. Otol Neurotol 2007;28:204–7CrossRefGoogle Scholar
26Olszewska, E, Lautermann, J, Koc, C, Schwaab, M, Dazert, S, Hildmann, H et al. Cytokeratin expression pattern in congenital and acquired pediatric cholesteatoma. Eur Arch Otorhinolaryngol 2005;262:731–6CrossRefGoogle ScholarPubMed
27Olszewska, E, Sudhoff, H. Comparative cytokeratin distribution patterns in cholesteatoma epithelium. Histol Histopathol 2007;22:37–42Google ScholarPubMed
28Park, HR, Min, SK, Min, K, Jun, SY, Seo, J, Kim, HJ. Increased expression of p63 and survivin in cholesteatomas. Acta Otolaryngol 2009;129:268–72CrossRefGoogle ScholarPubMed
29Kuczkowski, J, Bakowska, J, Pawelczyk, T, Narozny, W, Mikaszewski, B. Cell cycle inhibitory protein p27 in human middle ear cholesteatoma. ORL J Otorhinolaryngol Relat Spec 2006;68:296–301CrossRefGoogle ScholarPubMed
30Sakamoto, T, Kondo, K, Yamasodba, T, Suzuki, M, Sugasawa, M, Kaga, K. Over-expression of ErbB-2 protein in middle ear cholesteatomas. Laryngoscope 2004;114:1988–91CrossRefGoogle Scholar
31Osturk, K, Yildirim, MS, Ascar, H, Cenik, Z, Keles, B. Evaluation of c-myc status in primary acquired cholesteatoma by using fluorescence in situ hybridization techniques. Otol Neurotol 2006;27:588–91CrossRefGoogle Scholar
32Motamed, M, Powe, D, Kendall, C, Birchall, JP, Banerjee, AR. p53 Expression and keratinocyte hyperproliferation in middle ear cholesteatoma. Clin Otolaryngol Allied Sci 2002;27:505–8CrossRefGoogle ScholarPubMed
33Huang, CC, Chen, CT, Huang, TS, Shinoda, H. Mediation of signal transduction in keratinocytes of human middle ear cholesteatoma by ras protein. Eur Arch Otorhinolaryngol 1996;253:385–9CrossRefGoogle ScholarPubMed
34Miyao, M, Shinoda, H, Takahashi, S. Caspase-3, caspase-8 and nuclear factor-kappa beta expression in human cholesteatoma. Otol Neurotol 2006;27:8–1CrossRefGoogle ScholarPubMed
35Jung, MH, Lee, JH, Cho, JG, Jung, HH, Hwang, SJ, Chae, SW. Expressions of caspase-14 in human middle ear cholesteatoma. Laryngoscope 2008;118:1047–50CrossRefGoogle ScholarPubMed
36Huisman, MA, De Heer, E, Grote, JJ. Terminal differentiation and mitogen-activated protein kinase signaling in human cholesteatoma epithelium. Otol Neurotol 2006;27:422–6CrossRefGoogle ScholarPubMed
37Huisman, MA, De Heer, E, Grote, JJ. Survival signaling and terminal differentiation in cholesteatoma epithelium. Acta Otolaryngol 2007;127:424–9CrossRefGoogle ScholarPubMed
38Niam, R, Chang, RC, Sadick, H, Bayerl, C, Bran, G, Hormann, K. Effect of vascular endothelial growth factor on fibroblasts from external auditory canal cholesteatoma. Arch Med Res 2005;36:518–23CrossRefGoogle Scholar
39Morales, SD, Penido N de, O, da Silva, NID, Stavale, JN, Guilherme, A, Fukuda, Y. Matrix metalloproteinase 2: an important genetic marker for cholesteatomas. Braz J Otorhinolaryngol 2007;73:51–7CrossRefGoogle ScholarPubMed
40Song, JJ, Chae, SW, Woo, JS, Lee, HM, Jung, HH, Hwang, SJ. Differential expression of human beta defensin 2 and human beta defensin 3 in human middle ear cholesteatoma. Ann Otol Rhinol Laryngol 2007;116:235–40CrossRefGoogle ScholarPubMed
41Hussein, MRA, Sayed, RM, Abu-Dief, EE. Immune cell profile in invasive cholesteatomas: preliminary findings. Exp Mol Pathol 2010;88:316–23CrossRefGoogle ScholarPubMed
42Huisman, MA, de Heer, E, Dijke, PT, Grote, JJ. Transforming growth factor beta and wound healing in human cholesteatoma. Laryngoscope 2007;118:94–8CrossRefGoogle Scholar
43Jung, JY, Chole, RA. Bone resorption in chronic otitis media: the role of the osteoclast. ORL J Otorhinolaryngol Relat Spec 2002;64:95–107CrossRefGoogle ScholarPubMed
44Olszweska, E, Borzym-Kluczyk, M, Olszweska, S, Rogowski, M, Zwierz, K. Hexosaminidase as a new potential marker for middle ear cholesteatoma. Clin Biochem 2006;39:1088–90CrossRefGoogle Scholar
45Vitale, RF, Ribeiro F de, AQ. The role of tumor necrosis factor-alpha in bone resorption present in middle ear cholesteatoma. Bras J Otorrinolaringol 2007;73:123–7CrossRefGoogle ScholarPubMed
46Yuan, J, Akiyama, M, Nakahama, K-I, Sato, T, Uematsu, H, Morita, I. The effects of polyunsaturated fatty acids and their metabolites on osteoclastogenesis in vitro. Prostaglandins Other Lipid Mediat 2010;92:85–90CrossRefGoogle ScholarPubMed
47Byun, JY, Yune, TY, Lee, JY, Yeo, SG, Park, MS. Expression of CYLD and NF-κB in human cholesteatoma epithelium. Mediators Inflamm 2010;2010:796315. Epub 2010 Apr 21CrossRefGoogle ScholarPubMed
48Iino, Y, Toriyama, M, Ogawa, H, Kawakami, M. Cholesteatoma debris as an activator of human monocytes. Acta Otolaryngol (Stockh) 1990;110:410–15CrossRefGoogle ScholarPubMed
49Nason, R, Jung, JY, Chole, RA. Lipopolysaccharide-induced osteoclastogenesis from mononuclear precursors: a mechanism for osteolysis in chronic otitis. J Assoc Res Otolaryngol 2009;10:151–60CrossRefGoogle ScholarPubMed
50Hellstrom, S, Eriksson, PQ, Yoon, YJ, Johansson, U. Interactions between the middle ear and the inner ear: bacterial products. Ann N Y Acad Sci 1997;830:110–19CrossRefGoogle ScholarPubMed
51Aggarwal, BB, Shishodia, S, Sandur, SK, Pandey, MK, Sethi, G. Inflammation and cancer: how hot is the link? Biochem Pharmacol 2006;72:1605–21CrossRefGoogle ScholarPubMed
52Valko, M, Leibfritz, D, Moncol, J, Cronin, MTD, Mazur, M, Telser, MJ. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44–84CrossRefGoogle ScholarPubMed
53Eskiizmir, G, Yuceturk, AV, Onur, E, Var, A, Temiz, P. The imbalance of enzymatic antioxidants in cholesteatoma. Acta Otolaryngol 2009;129:1187–91CrossRefGoogle ScholarPubMed
54Online textbook of bacteriology. In: http://textbookofbacteriology.net [30 January 2012]Google Scholar
55Celebi, O, Paksoy, M, Aydin, S, Sanh, A, Tasdemir, O, Gull, AE. Myeloperoxydase activity in the pathogenesis of cholesteatoma. Indian J Otolaryngol Head Neck Surg 2010;62:32–5CrossRefGoogle ScholarPubMed
56Horrobin, DF. Medical uses of essential fatty acids. Vet Dermatol 1994;4:161–6CrossRefGoogle Scholar
57Das, UN. Essential fatty acids: a review. Curr Pharm Biotechnol 2006;7:467–82CrossRefGoogle ScholarPubMed
58Shah, US, Dhir, R, Golli, SM, Chandran, UR, Lewis, D, Acquafondata, M et al. Fatty acid synthase gene overexpression and copy number gain in prostate adenocarcinoma. Hum Pathol 2006;37:401–9CrossRefGoogle ScholarPubMed
59Martinasso, G, Oraldi, G, Trombetta, A, Maggiora, M, Bertetto, M. Involvement of PPARs in cell proliferation and apoptosis in human colon cancer specimens and in normal and cancer cell lines. PPAR Res 2007;2007:93416CrossRefGoogle ScholarPubMed
60Hwang, SJ, Kang, HJ, Song, JJ, Kang, JS, Woo, JS, Chae, SW et al. Up-regulation of peroxidase proliferator-activated receptor gamma in cholesteatoma. Laryngoscope 2006;116:58–61CrossRefGoogle ScholarPubMed
61Niki, E, Yoshida, Y, Saito, Y, Noguchi, N. Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 2005;338:668–76CrossRefGoogle ScholarPubMed
62Khan, M, Contreras, M, Sing, I. Endotoxin-induced alterations of lipid and fatty acid compositions in rat liver peroxisomes. J Endotoxin Res 2000;6:41–50CrossRefGoogle ScholarPubMed
63Knowles, HJ, Cleton-Jansen, A-M, Korsching, E, Athanasou, NA. Hypoxia-inducible factor regulates osteoclast-mediated bone resorption: role of angiopoietin-like 4. FASEB J 2010;24:4648–59Google ScholarPubMed
64O'Shea, M, Bassagaya-Riera, J, Mohede, IC. Immunomodulatory properties of conjugated linoleic acid. Am J Clin Nutr 2004;79:1199S–1206SCrossRefGoogle ScholarPubMed
65Aggarwal, BB. Nuclear factor-kappa B: a transcription factor for all seasons. Expert Opin Ther Targets 2007;11:109–10CrossRefGoogle ScholarPubMed
66Jung, JY, Lin, AC, Ramos, LM, Faddis, BT, Chole, RA. Nitric oxide synthase I mediates osteoclast activity in vitro and in vivo. J Cell Biochem 2003;89:613–21CrossRefGoogle ScholarPubMed
67Deon, M, Garcia, MP, Sitta, A, Barschak, AG, Coelho, M, Graziela, O et al. Hexacosanoic acid and docosanoic acids plasma levels in patients with cerebral childhood and asymptomatic X-linked adrenoleukodystrophy: Lorenzo's effect. Metab Brain Dis 2008;23:43–9CrossRefGoogle ScholarPubMed