Abstract
In the clinical setting, pediatric cholesteatomas frequently behave more aggressively than similar lesions in adults. The reason for the difference in behavior is still unclear. The purpose of the present study was to investigate the cell to cell and epithelial–stroma interaction of acquired cholesteatoma in adults and children and search for differences on the cellular level, which might explain the different behavior of these lesions. Operative specimens of 54 patients [40 adults (average age of 39.7 years), 14 children (average age of 8.3 years)] who underwent primary surgery for an acquired cholesteatoma of the middle ear were examined by histopathology and DNA-image cytometry (DNA-ICM). Immunohistochemical investigations included expression of proliferation markers (proliferation cell nuclear antigen and MIB-1) along with cell surface markers reflecting the cell-to-cell interaction (i.e. α1β6-integrin, E-cadherin, I-CAM = CD54), and the epithelial to stroma interaction (i.e. αv and β3 intergin chains, V-CAM = CD106, CD44v6 and fibronectin). Pediatric cholesteatomas demonstrated higher incidence of acute inflammation and more extensive disease relative to those from the adults. Indices of DNA-ICM, however, revealed normal diploid DNA content in both groups. Higher proliferation scores occurred in the pediatric group compared to adult cholesteatoma. Cell surface markers and cell adhesion molecules were equally expressed in both groups except α1β6-integrin and fibronectin, which were over expressed in pediatric cholesteatomas. Statistically, however, these differences showed only a trend towards significance. According to the results of the present study, pediatric and adult cholesteatomas do not show any marked differences on the cellular level. Thus the observed clinical more aggressive behavior of pediatric cholesteatoma is likely due to other secondary factors such as more intense inflammation, disturbed middle ear ventilation or the diminished calcium salt content of pediatric bone.
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References
Albino AP, Kimmelman CP, Parisier SC (1998) Cholesteatoma: a molecular and cellular puzzle. Am J Otol 19:7–19
Stammberger M, Bujia J, Kastenbauer E (1995) Alteration of epidermal differentiation in middle ear cholesteatoma. Am J Otol 16:527–531
Sastry KV, Sharma SC, Mann SB, Ganguly NK, Panda NK (1999) Aural cholesteatoma: role of tumor necrosis factor-alpha in bone destruction. Am J Otol 20:158–161
Amar MS, Wishahi HF, Zakhary MM (1996) Clinical and biochemical studies of bone destruction in cholesteatoma. J Laryngol Otol 110:534–539
Yan SD, Huang CC (1991) The role of tumor necrosis factor-alpha in bone resorption of cholesteatoma. Am J Otolaryngol 12:83–89
Shohet JA, de Jong AL (2002) The management of pediatric cholesteatoma. Otolaryngol Clin North Am 35:841–851
Mallet Y, Nouwen J, Lecomte-Houcke M, Desaulty A (2003) Aggressiveness and quantification of epithelial proliferation of middle ear cholesteatoma by MIB1. Laryngoscope 113:328–331
Feulgen R, Rossenbeck H (1924) Mikroskopisch chemischer Nachweis einer Nucleinsäure vom Typus der Thymonucleinsäure und die darauf beruhende elektive Färbung von Zellkernen in mikroskopischen Präparaten. Z Physiol Chem 135:203–248
Böcking A (1990) DNA-cytometry and automation in clinical diagnosis. Verh Dtsch Ges Pathol 74:176–185
Lang S, Nerlich A, Wiest I, Schreiner M (1994) Immunohistochemical analysis of the basement membrane in cholesteatoma epithelium. Laryngorhinootol 73:371–374
Marenda SA, Aufdemorte TB (1995) Localization of cytokines in cholesteatoma tissue. Otolaryngol Head Neck Surg 112:359–368
Hamzei M, Ventriglia G, Hagnia M, Antonopolous A, Bernal Sprekelsen M, Dazert S, Hildmann H, Sudhoff H (2003) Osteoclast stimulating and differentiating factors in human cholesteatoma. Laryngoscope 113:436–442
Sudhoff H, Bujia J, Borkowski G, Koc C, Holly A, Hildmann H, Fisseler-Eckhoff A (1996) Basement membrane in middle ear cholesteatoma. Immunohistochemical and ultrastructural observations. Ann Otol Rhinol Laryngol 105:804–810
Huang D, Han D (2003) Clinic feathers of cholesteatoma in children. Lin Chuang Er Bi Yan Hou Ke Za Zhi 17:193–195
Lavezzi A, Mantovani M, Cazzulo A, Turconi P, Matturri L (1998) Significance of trisomy 7 related to PCNA index in cholesteatoma. Am J Otolaryngol 19:109–112
Desloge RB, Carew JF, Finstad CL, Steiner MG, Sassoon J, Levenson MJ, Staiano-Coico L, Parisier SC, Albino AP (1997) DNA analysis of human cholesteatomas. Am J Otol 18:155–159
Jacob R, Welkoborsky HJ, Mann WJ (2001) Epithelium–stroma interaction in cholesteatoma of the middle ear. Laryngorhinootologie 80:11–17
Cui Y, Pan H, Gao Q (2001) DNA character of cholesteatoma. Lin Chuang Er Bi Yan Hou Ke Za Zhi 15:62–63
Motamed M, Powe D, Jones L, Kendall C, Banerjee AR (2000) Are p53 and MIB-1 overexpressed in cholesteatoma? Clin Otolaryngol 25:570–576
Motamed M, Powe D, Kendall C, Birchall JP, Banerjee AR (2002) P53 expression and keratinocyte hyperproliferation in middle ear cholesteatoma. Clin Otolaryngol 27:505–508
Huisman MA, De Heer E, Grote JJ (2003) Cholesteatoma epithelium is characterized by increased expression of Ki-67, p53 and p21, with minimal apoptosis. Acta Otolaryngol 123:377–382
Yu Q, Jin K (2001) A study on the state of cell proliferation and apoptosis in human middle ear cholesteatoma. Lin Chuang Er Bi Yan Hou Ke Za Zhi 15:450–451
Olszewska E, Chodynicki S, Chyczewski L (2003) Evaluation of epithelial proliferation and apoptosis in cholesteatoma of adults. Otolaryngol Pol 57:85–89
Durko M, Kaczmarczyk D (2004) Proliferation activity and apoptosis in granulation tissue and cholesteatoma in middle ear reoperations. Folia Morphol (Warsz.) 63:119–121
Sudhoff H, Bujia J, Fisseler-Eckhoff A, Holly A, Schulz-Flake C, Hildmann H (1995) Expression of a cell-cycle-associated nuclear antigen (MIB1) in cholesteatoma and auditory meatal skin. Laryngoscope 105:1227–1231
Bernal Sprekelsen M, Ebmeyer J, Buchbinder A, Sudhoff H (2000) Comparative analysis of the proliferative capacity of cholesteatomas. Acta Otorrinolaryngol Esp 51:299–307
Hoppe F (1995) An investigation of the proliferation potential in cholesteatoma. HNO 43:710–715
Bujia J, Sudhoff H, Holly A, Hildmann H, Kastenbauer E (1996) Immunohistochemical detection of proliferating cell nuclear antigen in middle ear cholesteatoma. Eur Arch Otorhinolaryngol 253:21–24
Tanaka Y, Shiwa M, Kojima H, Miyazaki H, Kamide Y, Moriyama H (1998) A study on epidermal proliferation ability in cholesteatoma. Laryngoscope 108:537–542
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 37:118–120
Hassmann-Poznanska E, Skotnicka B, Dzieciol J (2003) Markers of epidermal proliferation in middle ear cholesteatoma. Otolaryngol Pol 57:505–511
Maraki D, Becker J, Boecking A (2004) Cytologic and DNA-cytometric very early diagnosis of cancer. J Oral Pathol Med 33:398–404
Welkoborsky HJ, Gluckman JL, Jacob R, Bernauer H, Mann WJ (1999) Tumorbiologic prognostic parameters in T1N0M0 squamous cell carcinoma of the oral cavity. Larnygorhinootol 78:131–138
Yildirim MS, Ozturk K, Acar H, Arbag H, Ulku CH (2003) Chromosome 8 aneuploidy in acquired cholesteatoma. Acta Otolaryngol 123:372–376
Rao VV, Schnittger S, Hansmann I (1991) Chromosomal localization of the human proliferating cell nuclear antigen (PCNA) gene to or close to 20p12 by in situ hybridization. Cytogenet Cell Genet 56:169–170
Taniguchi Y, Katsumata Y, Koido S, Suemizu H, Yoshimura S, Moriuchi T, Okumura K, Kagotani K, Taguchi H, Imanishi T, Gojobori T, Inoko H (1996) Cloning, sequencing, and chromosomal localization of two tandemly arranged human pseudogenes for the proliferating cell nuclear antigen (PCNA). Mamm Genome 7:906–908
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 262:731–736
Breitkreutz D, Stark HJ, Mirancea N, Tomakidi P, Steinbauer H, Fusenig NE (1997) Integrin and basement membrane normalization in mouse grafts of human keratinocytes—implications for epidermal hemostasis. Differentiation 61:195–209
Naim R, Riedel F, Bran G, Hormann K (2003) Expression of beta-catenin in external auditory canal cholesteatoma. Biofactors 19:189–195
Akimoto R, Pawankar R, Yagi T, Baba S (2000) Acquired and congenital cholesteatoma: determination of tumor necrosis factor-alpha, intercellular adhesion molecule-1, interleukin-1-alpha and lymphocyte functional antigen-1 in the inflammatory process. ORL J Otorhinolaryngol Relat Spec 62:257–265
Kim HJ, Tinling SP, Chole RA (2001) Expression patterns of cytokeratin in retraction pocket cholesteatomas. Laryngoscope 111:1032–1036
Yetiser S, Satar B, Aydin N (2002) Expression of epidermal growth factor, tumor necrosis factor-alpha, and inetrleukin-1 alpha in chronic otitis media with or without cholesteatoma. Otol Neurotol 23:647–652
Dallari S, Cavani A, Bergamini G, Girolomoni G (1994) Integrin expression in middle ear cholesteatoma. Acta Otolaryngol 114:188–192
Shinoda H, Huang CC (1995) Localization of intercellular adhesion molecule-1 in middle ear cholesteatoma. Eur Arch Otorhinolaryngol 252:385–390
Bujia J, Holly A, Stammberger M, Sudhoff H (1996) Angiogenesis in cholesteatoma of the middle ear. Acta Otorrinolaringol Esp 47:187–192
Schilling V, Holly A, Bujia J, Schulz P, Kastenbauer E (1995) High levels of fibronectin in the stroma of aural cholesteatoma. Am J Otolaryngol 16:232–235
Bernal Sprekelsen M, Ebmeyer J, Anonopoulos A, Borkowski G, Sudhoff H (2001) Alterations of the basal membrane in middle ear cholesteatoma. Acta Otorrinolaryngol Esp 52:330–335
Yamamoto-Fukuda T, Aoki D, Hishikawa Y, Kobayashi, Takahashi H, Koji T (2003) Possible involvement of keratinocyte growth factor and its receptor in enhanced epithelial-cell proliferation and acquired recurrence of middle-ear cholesteatoma. Lab Invest 83:123–136
Banerjee AR, Jones JL, Birchall JP, Powe DG (2001) Localization of matrix metalloproteinase 1 in cholesteatoma and deep meatal skin. Otol Neurotol 22:579–581
Bayazit YA, Karakok M, Ucak R, Kanlikama M (2001) Cycline-dependent kinase inhibitor, p27 (KIP1), is associated with cholesteatoma. Laryngoscope 111:1037–1041
Wilmoth JG, Schultz GS, Antonelli PJ (2003) Tympanic membrane metalloproteinase inflammatory response. Otolaryngol Head Neck Surg 129:647–654
Wilmoth JG, Schultz GS, Antonelli PJ (2003) Matrix metalloproteinases in a gerbil cholesteatoma model. Otolaryngol Head Neck Surg 129:402–407
Tokuriki M, Noda I, Saito T, Narita N, Sunaga H, Tsuzuki H, Ohtsubo T, Fujieda S, Saito H (2003) Gene expression analysis of human middle ear cholesteatoma using complementary DNA arrays. Laryngoscope 113:808–814
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Welkoborsky, HJ., Jacob, R.S. & Hinni, M.L. Comparative analysis of the epithelium stroma interaction of acquired middle ear cholesteatoma in children and adults. Eur Arch Otorhinolaryngol 264, 841–848 (2007). https://doi.org/10.1007/s00405-007-0328-7
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DOI: https://doi.org/10.1007/s00405-007-0328-7