Abstract
The aim of this study was to determine the distribution and apoptotic capacity in the various layers of cholesteatoma epithelium compared to the normal skin. Cholesteatomas were collected during surgical procedures of the ear. Normal skin specimens taken from the retroauricular area served as controls. Apoptosis was detected by using highly specific antibodies against APO2.7 antigen. The Membstain Apoptosis kit Direct based on in situ labeling of nuclear DNA fragmentation (Tolt-mediated dUTP nick and labeling TUNEL staining) was used. The distribution of apoptotic cells in the layer of the cholesteatoma epithelium and the epidermis was determined. The percentage of apoptotic cells was then counted per 100 cells of cholesteatoma epithelium and the normal epidermis in three different areas of each section and expressed in terms of mean ± SD. An automatic analyzing system was used for counting. In normal epidermis, the apoptotic cells were observed in the granular layer of the epidermis. The percentage of these cells was 28.5±8.1%. A significantly greater number of apoptotic cells was observed in the suprabasal layers of the cholesteatoma epithelium (47.39±6.2%). A statistically significant difference was obtained for APO2.7-positive cells in the cholesteatoma epithelium as compared to the skin (P<0.05) as determined by Student’s t-test and the Mann-Whitney U test. Apoptotic activity is mainly observed in the suprabasal layer of cholesteatoma epithelium. It is not seen in the basal layer. Apoptosis plays an important role in the pathogenesis of cholesteatoma. It seems to be part of the differentiation and accumulation of keratin debris within the middle ear and expansion of cholesteatoma.
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References
Akahami S, Nangia- Makker P, Inohara H, Kim HR, Raz A (1997) Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res 57:5272–5276
Albino AP, Reed JA, Bogdany JK, Sassoon J, Desloge RB, Parisier SC (1998) Expression of p53 protein in human middle ear cholesteatomas: pathogenetic implications. Am J Otol 19:30–36
Alison MR, Sarraf CE (1992) Apoptosis: a gene-directed programme of cell death. Roy Coll Phys London 26:25–35
Bujía J, Holly A, Sudhoff H, Antoli-Candela F, Tapia MG, Kastenbauer E (1996) Identification of proliferating keratinocytes in middle ear cholesteatoma using the monoclonal antibody Ki-67. ORL 58:23–26
Bujia J, Sudhoff H, Holly A, Hildmann H, Kastenbauer E (1996) Immunohistochemical detection of proliferating cell nuclear antigen middle ear cholesteatoma. Eur Arch Otorhinolaryngol 253:21–24
Choufani G, Mahillon V, Decaestecker C, Lequeux T, Danguy A, Salmon I, Gabius H-J, Hassid S (1999) Determination of the levels of expression of sarcolectin and calcyclin and of percentages of apoptotic but not proliferating cells to enable distinction between recurrent and nonrecurrent cholesteatomas. Laryngoscope 109:1825–1831
Cooper DN, Barondes SH (1999) God must love galectins; he made so many of them. Glycobiology 9:979–984
Ergun S, Carsloo B, Zheng X (1999) Apoptosis in meatal skin, cholesteatoma and squamous cell carcinoma of the ear. Clin Otolaryngol 24:280–285
Kojima H, Tanaka Y, Toshihide T, Miyazaki H, Shiwa M, Kamide Y, Moriyama H (1998) Cell proliferation and apoptosis in human middle ear cholesteatoma. Arch Otolaryngol Head Neck Surg 124:261–264
Michaels L (1987) Cholesteatoma. Ear nose throat histopthology. Springer, New York Heidelberg Berlin
Miyazaki H, Kojima H, Shiwa M, Koga T, Moriyama H (1999) Terminal differentiation of epithelial cells in middle ear cholesteatoma: investigation of patterns of expression of protein kinase C-δ and protein kinase C-η. Laryngoscope 109:1785–1792
Olszewska E, Lautermann J, Koc C, Schwaab M, Dazert S, Hildmann H, Sudhoff H (2005) Cytokeratin expression pattern in congenital and acquired pediatric cholesteatoma. Eur Arch Otorhinolaryngol 262(9):731–736
Olszewska E, Wagner M, Mernal-Sprekelsen M, Ebmeyer J, Dazert S, Hildmann H, Sudhoff H (2003) Etiopathogenesis of cholesteatoma. Eur Arch Otorhinolaryngol 261:6–24
Olszewska E, Chodynicki S, Chyczewski L (2003) Assessment of proliferation and apoptosis in cholesteatoma epithelium in adults. Otolaryngol Pol LVII:85–89
Park HJ, Park K (1999) Expression of Fas/APO-1 and apoptosis of keratinocytes in human cholesteatoma. Laryngoscope 109:613–616
Polakowska RP, Placentini M, Bartlett R, Goldsmith LA, Haake AR (1994) Apoptosis in human skin development: morphogenesis periderm, and stem cells. Dev Dyn 199:176–188
Sheikholeslam-Zadeh R, Decaestecker C, Delbrouck C, Danguy A, Salmon I, Zick, Kaltner H, Hassid S, Gabius H-J, Kiss R, Choufani G (2001) The levels of expression of galectin-3, but not of galectin-1 and galectin-8, correlate with apoptosis in human cholesteatomas. Laryngoscope 111:1042–1047
Shinoda H, Huang C-C (1995) Expressions of c-jun and p53 proteins in human middle ear cholesteatoma: relationship to keratinocyte proliferation, differentiation and programmed cell death. Laryngoscope 105:1232–1237
Svane-Knudsen V, Halkier-Sorensen L, Rasmussen G, Ottosen PD (2001) Cholesteatoma: a morphologic study of stratum corneum lipids. Acta Otolaryngol 121:602–606
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Olszewska, E., Chodynicki, S. & Chyczewski, L. Apoptosis in the pathogenesis of cholesteatoma in adults. Eur Arch Otorhinolaryngol 263, 409–413 (2006). https://doi.org/10.1007/s00405-005-1026-y
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DOI: https://doi.org/10.1007/s00405-005-1026-y