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2018, vol. 75, br. 5, str. 487-495
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Značaj ekspresije markera ćelijske proliferacije i inflamacije u razvoju stečenog holesteatoma srednjeg uva
The significance of the expression of cell proliferation and inflammation markers in the development of acquired middle ear cholesteatoma
aVojnomedicinska akademija, Klinika za otorinolaringologiju, Beograd bUniverzitet u Beogradu, Medicinski fakultet, Institut za patološku anatomiju + Univerzitet odbrane, Medicinski fakultet Vojnomedicinske akademije, Beograd cUniverzitet u Beogradu, Medicinski fakultet, Institut za patološku anatomiju dVojnomedicinska akademija, Klinika za otorinolaringologiju, Beograd + Univerzitet odbrane, Medicinski fakultet Vojnomedicinske akademije, Beograd
e-adresa: j.sotirovic@gmail.com
Sažetak
Konstantna proliferacija i periodične infekcije su glavne kliničke karakteristike stečenog holesteatoma srednjeg uva. Cil ove studije bio je da se istraže imunohistohemijske karakteristike kože i holesteatomskog procesa u obližnjem tkivu i tako prostudira etiologija i razvoj stečenog holesteatoma srednjeg uva. Metode. Istraživali smo kliničke, histološke i imunohistohemijske karakteristike holesteatoma 50 operisanih bolesnika sa stečenim holesteatomom srednjeg uva. Klasifikovali smo sve uzorke prema kliničkim karakteristikama holesteatoma kao što su destrukcija kosti, prisustvo infekcije ili proširenost holesteatomskog procesa i histološkim karakteristikama holesteatoma kao što su keratinizacija, inflamatorni proces i ekstraćelijska proliferacija matriksa. Koristili smo mišija monoklonska antitela za proliferišući ćelijski nuklearni antigen (Mabs za PCNA), Ki-67, COX-2, CD 4 i CD 8 limfocite da bi istražili ekspresiju ovih karakteristika u holesteatomu i u kontrolnom tkivu kože. Statističke analize izvedene su korišćenjem SPSS za Windows, verzija 16.0 (SPSS, Chicago, IL, USA). Koristili smo t-test za nezavisne grupe, Spirmanovu analizu korelacije i Mann-Whitney U test za statističku analizu. Rezultati. Ekspresija PCNA, Ki67, COX-2 i CD 8 limfocita u holesteatomima sa težom kliničkom slikom bila je podjednaka kao u holesteatomima sa lakšom kliničkom slikom. Postojala je statistički značajno viša koncentracija CD4 limfocita u uzorcima stečenog holesteatoma i u uzorcima kože koštanog dela spoljnog slušnog hodnika, u blizini fibrokartilaginoznog anulusa, u holestetomima sa težom kliničkom slikom nego u holesteatomima sa lakšom kliničkom slikom (p < 0,05). Postojala je statistički značajna razlika ekspresije PCNA, Ki-67, COX-2, CD-4 i CD 8 limfocita između uzorka holesteatoma i uzoraka kože koštanog dela spoljnog slušnog kanala svih operisanih bolesnika (p < 0,05) i statistički značajna razlika u ekspresiji PCNA, Ki-67, COX-2, CD-4 i CD 8 limfocita u koži koštanog dela spoljnog slušnog hodnika u odnosu na retroaurikularnu kožu (p < 0,05). Zaključak. Inflamacija kože koštanog dela spoljnog slušnog hodnika je prekretnica u patogenezi stečenog holesteatoma srednjeg uva. Ekspresija CD4 limfocita može biti prognostički faktor u razvoju kliničke slike stečenog holesteatoma. Našli smo toliko različitosti u biološkom ponašanju holesteatoma na različitim nivoima kliničkog razvoja. Ekspresija Ki-67 u stečenom holesteatomu srednjeg uva je pouzdan i stabilan marker proliferacije stečenog holesteatoma.
Abstract
Permanent proliferation and periodical infection are the main clinical characteristics of acquired middle ear cholesteatoma. The aim of this study was to research immunohistochemical characteristics of the skin along with the cholesteatoma process in the nearby tissue. This research should influence further studying of etiology and development of acquired middle ear cholesteatoma. Methods. We investigated clinical, histological and immunohistochemical characteristics of cholesteatoma in 50 samples from operated patients with acquired middle ear cholesteatomas. We classified all samples according to their clinical characteristics of cholesteatoma such as bone destruction, presence of infection or cholesteatoma extension and histological characteristics of cholesteatoma such as keratinisation, inflammatory process and extracellular matrix proliferation. We used mouse monoclonal antibodies for proliferating cell nuclear antigen (MAbs for PCNA), Ki-67, COX-2, CD 4 and CD 8 lymphocytes to investigate the expression of those characteristics in the cholesteatoma and in the control skin tissue. Statistical analyses were performed using SPSS for Windows version 16.0 (SPSS, Chicago, IL, USA). We used the independent group t-test, Spearman's correlation analysis and Mann-Whitney U test to analyze statistical analysis. Results. Expression of PCNA, Ki-67, COX-2 and CD 8 lymphocytes in more serious clinical picture of cholesteatoma was almost equal as in less serious clinical picture of cholesteatoma. There was statistically significantly higher concentration of inflammation marker CD 4 lymphocytes, both in the acquired cholesteatoma and in the skin of bony portion of the external auditory canal near fibrocartilaginous annulus in more serious clinical picture of cholesteatoma than in less serious clinical picture of cholesteatoma (p < 0.01). There was statistically significant difference of expression of PCNA, Ki67, COX-2, CD 4 and CD 8 lymphocytes between all cholesteatoma samples and the skin of bony portion of the external auditory canal (p < 0.05) and statistically significant difference of expression of those markers between the skin of bony portion of the external auditory canal and retroauricular skin (p < 0.05). Conclusion. Inflammation of the skin of bony portion of the external auditory canal is a milestone in pathogenesis of acquired middle ear cholesteatoma. Expression of CD 4 lymphocytes can be the prognostic factor for acquired cholesteatoma clinical picture development. We found so much diversity in biological behavior through very different levels of cholesteatoma development. Expression of Ki-67 in acquired middle ear cholesteatoma is a reliable and stable marker of proliferation for acquired middle ear cholesteatoma.
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Reference
|
|
 
|
Alicandri-Ciufelli, M., Marchioni, D., Presutti, L. (2016) In response to A new theory on the pathogenesis of acquired cholesteatoma: Mucosal traction. Laryngoscope, 126(1): E48-9
|
|
|
Aslıer, M., Erdag, T.K., Sarioglu, S., Güneri, E.A., Ikiz, A.O., Uzun, E., Özer, E. (2016) Analysis of histopathological aspects and bone destruction characteristics in acquired middle ear cholesteatoma of pediatric and adult patients. International Journal of Pediatric Otorhinolaryngology, 82: 73-77
|
|
|
Bjarnsholt, T. (2013) The role of bacterial biofilms in chronic infections. APMIS, 121: 1-58
|
|
|
Dornelles, C., Meurer, L., da Costa, S.S., Schweiger, C. (2006) Histologic description of acquired cholesteatomas: comparison between children and adults. Brazilian Journal of Otorhinolaryngology, 72(5): 641-648
|
|
|
Erdoglija, M., Milanović, N., Čolić, M., Jović, M. (2014) Middle ear cholesteatoma: Correlation of histological, immunohistochemical and clinical characteristics. MD - Medical data, vol. 6, br. 4, str. 315-321
|
|
|
Frickmann, H. (2012) Cholesteatoma ? A Potential Consequence of Chronic Middle Ear Inflammation. Otolaryngology, 02(03): 2-8
|
|
|
Gray, J.D. (1964) The chronic ear. The treatment of cholesteatoma in children. Proc R Soc Med, 57: 769-71
|
|
|
Heikki, O. K.H.J. P. (1999) Epidemiology and Aetiology of Middle Ear Cholesteatoma. Acta Oto-Laryngologica, 119(5): 568-572
|
|
|
Huisman, M.A., de Heer, E., Grote, J.J. (2005) Sustained extracellular signal-regulated kinase1/2 mitogen-activated protein kinase signalling is related to increased p21 expression in cholesteatoma epithelium. Acta Oto-Laryngologica, 125(2): 134-140
|
|
|
Hussein, M.R.A., Sayed, R.H., Abu-Dief, E.E. (2010) Immune cell profile in invasive cholesteatomas: Preliminary findings. Experimental and Molecular Pathology, 88(2): 316-323
|
|
|
Kaya, E., Dag, I., Incesulu, A., Gurbuz, M.K., Acar, M., Birdane, L. (2013) Investigation of the Presence of Biofilms in Chronic Suppurative Otitis Media, Nonsuppurative Otitis Media, and Chronic Otitis Media with Cholesteatoma by Scanning Electron Microscopy. Scientific World Journal, 2013: 1-6
|
|
|
Li, H., Jiang, P., Wang, L. (2002) Immunohistochemical study of the epithelial hyperproliferation in middle ear cholesteatoma. Zhonghua Er Bi Yan Hou Ke Za Zhi, 37(2): 118-20 (Chinese)
|
|
|
Liu, L., Li, Z., Hu, M. (1995) Langerhans cells and human aural cholesteatoma. Zhonghua Er Bi Yan Hou Ke Za Zhi, 30(1): 33-6 (Chinese)
|
|
|
Ma, X., Yu, L.S., Xia, R.M. (2006) Immunohistochemical discrimination of aggressivity between the cholesteatoma from different positions. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 41(8): 574-8 (Chinese)
|
|
|
Maniu, A., Harabagiu, O. (2014) Perde Schrepler M, Cătană A, Fănuţă B, Mogoantă CA. Molecular biology of cholesteatoma. Rom J Morphol Embryol, 55(1): 7-13
|
|
|
Miyahara, N., Fukushima, N., Hirai, T., Miyoshi, A., Ariki, M. (2016) Clinical Features of the Pediatric Acquired Cholesteatoma Based on the Staging Criteria for Cholesteatoma 2010 Japan. Nippon Jibiinkoka Gakkai Kaiho, 119(3): 181-186
|
|
|
Ogino, S., Kirkner, G. J., Nosho, K., Irahara, N., Kure, S., Shima, K., Hazra, A., Chan, A. T., Dehari, R., Giovannucci, E. L., Fuchs, C. S. (2008) Cyclooxygenase-2 Expression Is an Independent Predictor of Poor Prognosis in Colon Cancer. Clinical Cancer Research, 14(24): 8221-8227
|
|
|
Park, K., Park, H., Chun, Y. (2001) Immunohistochemical study on proliferative activity of experimental cholesteatoma. European Archives of Oto-Rhino-Laryngology, 258(3): 101-105
|
|
|
Raynov, A.M., Moon, S., Choung, Y., Hong, S.P., Park, K. (2005) Nucleoplasm staining patterns and cell cycle-associated expression of Ki-67 in middle ear cholesteatoma. American Journal of Otolaryngology, 26(5): 296-301
|
|
|
Sade, J. (1993) Treatment of cholesteatoma and retraction pockets. Eur Arch Otorhinolaryngol, 250(4): 193-9
|
|
|
Sanli, A., Tezer, I., Paksoy, M., Aydin, S., Hardal, U., Ozdemir, N.B. (2007) Evaluation of Ki-67 expression in recurrent cases of cholesteatoma. Kulak Burun Bogaz Ihtis Derg, 17(2): 65-9, (Turkish)
|
|
|
Schluter, C. (1993) The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. Journal of Cell Biology, 123(3): 513-522
|
|
|
Songu, M., Altay, C., Onal, K., Arslanoglu, S., Balci, M.K., Ucar, M., Ciger, E., Kopar, A. (2015) Correlation of computed tomography, echo-planar diffusion-weighted magnetic resonance imaging and surgical outcomes in middle ear cholesteatoma. Acta Oto-Laryngologica, 135(8): 776-780
|
|
|
Starborg, M., Gell, K., Brundell, E., Höög, C. (1996) The murine Ki-67 cell proliferation antigen accumulates in the nucleolar and heterochromatic regions of interphase cells and at the periphery of the mitotic chromosomes in a process essential for cell cycle progression. J Cell Sci, 109 ( Pt 1): 143-53
|
|
|
Welkoborsky, H.J. (2011) Current concepts of the pathogenesis of acquired middle ear cholesteatoma. Laryngorhinootologie, 90(1): 38 ̶ 48; quiz 49-50. (German)
|
|
|
|
|