Abstract
Aim To investigate the immunohistochemical expression of Ki-67, p53 and p63 in Keratocyst Odontogenic Tumours (KOTs) in order to contribute to the biological profile of this tumor. Methods Immunohistochemical technique was performed using the EnVision™ System in 37 cases of KOTs. Results Ki-67- and p53-immunostained cells were mainly located in the suprabasal layers. p63-positive cells were found throughout the lining cystic epithelium. No difference in the immunostaining for these proteins was observed between primary and recurrent KOTs (Ki-67: P = 0.5591; p53: P = 0.9847; p63: P = 0.9127), or between KOTs associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) and sporadic KOTs (Ki-67: P = 0.7013; p53: P = 0.3197; p63: P = 0.2427). Conclusions It is possible that biological behavior of KOTs may be related to suprabasal proliferative compartment in the cystic epithelium as observed by high levels of Ki-67, p53 and p63. In addition, p63 immunostaining may represent immaturity of keratinocytes in KOTs, and suggests that this protein may participate in the regulation of epithelial cell differentiation. Taken together, these data may favor tumorigenesis on KOTs.
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References
Agaram N, Collins B, Barnes L et al (2004) Molecular analysis to demonstrate that odontogenic keratocysts are neoplastic. Arch Pathol Lab Med 128:313–317
Barbiere C, Pietenpol J (2005) p63 and epithelial biology. Exp Cell Res 312:695–706
Caserta T, Kommagani R, Yuan Z et al (2006) p63 overexpression induces the expression of Sonic Hedgehog. Mol Cancer Res 4:759–768
De Laurenzi V, Rossi A, Terrinoni A et al (2000) p63 and p73 transactivate differentiation gene promoters in human keratinocytes. Biochem Biophys Res 273:342–346
De Luca M, Pellegrini G, Green H (2006) Regeneration of squamous epithelium from stem cells of cultured grafts. Regenerative Med 1:45–57
De Paula A, Carvalhais J, Domingues M et al (2000) Cell proliferation markers in the odontogenic keratocyst. J Oral Pathol Med 29:477–482
Foschini M, Cocchi R, Marucci G et al (2006) High deltaN p63 isoform expression favours recurrences in odontogenic keratocyst-odontogenic keratocyst tumour. Int J Oral Maxilllofac Surg 35:673–675
Gerdes J, Li L, Schlueter L et al (1991) Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 138:867–873
Giuliani M, Grossi G, Lajolo C et al (2006) Conservative Management of a large Odontogenic Keratocyst: Report of a case and review of the literature. J Oral Maxillofac Surg 64:308–316
Gonzalez-Moles M, Mosqueda-Taylor A, Delgado-Rodriguez M et al (2006) Analysis of p53 protein by PAb240, Ki-67 expression and papillomavirus DNA detection in different types of odontogenic keratocyst. Anticancer Res 26:175–181
Henley J, Summerlin D, Tomich C et al (2005) Molecular evidence supporting the neoplastic nature of odontogenic keratocyst: a laser microdissection study of 15 cases. Histopathology 46:582–586
Kaplan I, Hirshberg A (2004) The correlation between epithelial cell proliferation and inflammation in odontogenic keratocyst. Oral Oncol 40:985–991
Kochaji N, Goossens A, Geerts A, Bootenberg P (2005) PTCH expression in odontogenic cysts, a cause of pathogenesis or reason for clinical complication. Oral Oncol 41:284–288
Kolar Z, Geierova M, Bouchal J et al (2006) Immunohistochemical analysis of the biological potential of odontogenic keratocysts. J Oral Pathol Med 35:75–80
Kichi E, Enokiya Y, Muramatsu T et al (2005) Cell proliferation, apoptosis and apoptosis-related factors in odontogenic keratocysts and in dentigerous cysts. J Oral Pathol Med 34:280–286
Kim D, Ahn S, Kim J, Yoon J (2003) Comparative Ki-67 expression and apoptosis in the odontogenic keratocyst associated with or without an impacted tooth in addition to unilocular and multilocular varieties. Yonsei Medical J 44:841–846
Kimi K, Kumamoto H, Ooya K, Motegi K (2000) Immunohistochemical analysis of cell-cycle-and apoptosis-related factors in lining epithelium of odontogenic keratocysts. J Oral Pathol Med 30:434–442
Lane D (1992) Worrying about p53. Curr Biol 2:581–583
Levine A, Momande J, Finlay C (1991) The p53 tumour suppressor gene. Nature 6:453–456
Li TJ, Browne R, Matthews J (1995) Epithelial cell proliferation in odontogenic keratocyst: a comparative immunohistochemical study of ki-67 in simple, recurrent and basal cell nevus syndrome (BCNS)-associated lesions. J Oral Pathol Med 24:221–226
Li TJ, Browne R, Prime S et al (1996) p53 expression in odontogenic keratocyst epithelium. J Oral Pathol Med 25:249–255
Little N, Jochemsen A (2002) p63. Int J Biochem Cell Biol 34:6–9
Lo Muzio L, Staibano S, Pannone G et al (1999) Expression of Cell Cycle and Apoptosis-related Proteins in Sporadic Odontogenic Keratocysts and Odontogenic Keratocysts associated with the Nevoid Basal Cell Carcinoma Syndrome. J Dent Res 78:1345–1353
Lo Muzio L, Santarelli R, Caltabiano C et al (2005) p63 expression in odontogenic cysts. Int J Oral Maxillofac Surg 34:668–673
Lombardi T, Odell E, Morgan P (1995) p53 Immunohistochemistry of odontogenic keratocysts in relation to recurrence, basal-cell budding and basal-cell naevus syndrome. Arch Oral Biol 40:1081–1084
McCormick D, Chong H, Hobbs C et al (1993) Detection of the Ki-67 antigen in fixed and wax-embedded sections with the monoclonal antibody MIB1. Histopathology 22:355–360
Mills A (2006) p63: Oncogene or tumor suppressor? Curr Opin Genet Develop 16:1–7
Morgunkova A (2005) The p53 gene family: Control of cell proliferation and development programs. Biochemistry (Moscow) 70:955–971
Nylander K, Coates P, Hall P (2002) Differential expression of p63 isoforms in normal tissue and neoplastic cells. J Pathol 198:417–427
Oda D, Rivera V, Ghanne N et al (2000) Odontogenic keratocyst: the northwestern USA experience. J Contemp Dental Pract 1:60–74
Ogden G, Chisholm R et al (1992) p53 protein in odontogenic cysts: Increased expression in some odontogenic keratocyst. J Clin Pathol 45:1007–1010
Parsa R, Yang A, McKeon F, Green H (1999) Association of p63 with proliferative potential in normal and neoplastic human keratinocytes. J Invest Dermatol 113:1099–1105
Philipsen H P (2005) Keratocyst odontogenic tumour. In: WHO Classification of tumours. Head and Neck tumours, IARC press, Lyon, pp 306–307
Piattelli A, Foroni M, Santinelli A, Rubini C (2001) p53 expression in odontogenic cysts. J Endodontics 27:459–461
Save V, Nylander K, Hall P (1998) Why is p53 protein stabilized in neoplasia? Some answers but many more questions! J Pathol 184:348–350
Senoo M, Pinto F, Crum C, McKeon F (2007) p63 is essential for the proliferative potential of stem cells in stratified epithelia. Cell 129:523–536
Shear M (2002a) The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 1 Clinical and early experimental evidence of aggressive behaviour. Oral Oncol 38:219–226
Shear M (2002b) The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 2 Proliferation and genetic studies. Oral Oncol 38:323–331
Shear M (2002c) The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 3 Immunocytochemistry of cytokeratin and other epithelial cell markers. Oral Oncol 38:407–415
Slootweg P (1995) p53 and Ki-67 reactivity in epithelial odontogenic lesion. An Immunohistochemical study. J Oral Pathol Med 24:393–397
Stoelinga P (2001) Long-term follow-up on keratocysts treated according to a defined protocol. Int J Oral Maxillofac Surg 30:14–25
Thosaporn W, Iamaroon A, Pongsiriwet S, Ng K (2004) A comparative study of epithelial cell proliferation between the odontogenic keratocyst, orthokeratinized odontogenic cyst, dentigerous cyst and ameloblastoma. Oral Dis 10:22–26
Verheijen R, Kuijpers H, Schlingemman R et al (1989) Ki-67 detects a nuclear matrix-associated proliferation-related antigen. I. Intracellular localization during interphase. J Cell Science 92:123–130
Yang A, Kaghad M, Wang Y et al (1998) p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2:305–316
Yang A, Kaghad M, Wang Y et al (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398:714–718
Yang A, Kaghad M, Caput D, McKeon F (2002) On the shoulders of giants: p63, p73 and the rise of p53. Trends Genet 8:90–95
Acknowledgments
We thank Ana Cristina Mota, Nancy Silva Santos for excellent technical assistance. This study was supported by CNPq, and grants from FAPESB No. 200/04.
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Gurgel, C.A.S., Ramos, E.A.G., Azevedo, R.A. et al. Expression of Ki-67, p53 and p63 proteins in keratocyst odontogenic tumours: an immunohistochemical study. J Mol Hist 39, 311–316 (2008). https://doi.org/10.1007/s10735-008-9167-0
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DOI: https://doi.org/10.1007/s10735-008-9167-0