Biological pathways involved in the aggressive behavior of the keratocystic odontogenic tumor and possible implications for molecular oriented treatment - An overview

In the classification of Head and Neck Tumors, published in 2005 by the World Health Organization Classification, the odontogenic keratocyst has been reclassified as a benign intraosseous neoplasm, calling it "keratocystic odontogenic tumor" (KCOT). Significant differences on the molecular level between KCOT and other odontogenic cystic lesions suggest a different biological origin. Genetic and molecular research regarding odontogenic tumors, and KCOTs in particular, has led to an increasing amount of knowledge and understanding of their physiopathological pathways. A review of the biological behavior of this recognized aggressive pathological entity of the jaws and a contemporary outline of the molecular (growth factors, p53, PCNA and Ki-67, bcl-2) and genetic (PTCH, SHH) alterations associated with this odontogenic neoplasm provides a better understanding of the mechanisms involved in its development and strengthen the current concept that the KCOT should, indeed, be regarded as a neoplasm. Furthermore, markers known to be rapidly induced in response to growth factors, tumor promoters, cytokines, bacterial endotoxins, oncogenes, hormones and shear stress, such as COX-2, may also shed new light on the biological mechanisms involved in the development of these benign but sometimes aggressive neoplasms of the jaws. (C) 2009 Elsevier Ltd. All rights reserved.