Metallothionein in the radicular, dentigerous, orthokeratinized odontogenic cysts and in keratocystic odontogenic tumor Aline Cristina Batista Rodrigues Johann 1 , Patrı´cia Carlos Caldeira 2 , Marcelo Vidigal Caliari 3 , Mauro Henrique Nogueira Guimara˜es de Abreu 4 , Maria Ca´ssia Ferreira Aguiar 2 , Ricardo Alves Mesquita 2 1 Department of Stomatology, School of Dentistry, Pontifı´cia Universidade Cato ´lica do Parana ´, Curitiba, PR, Brazil; 2 Department of Oral Surgery, Oral Medicine, and Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, MG, Brazil; 3 Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, MG, Brazil; 4 Department of Community and Preventive Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, MG, Brazil BACKGROUND: Metallothionein (MT) is a protein cor- related with cellular differentiation and proliferation, as well as with the inhibition of apoptosis. The aims were to report and to compare the MT expression in odontogenic cysts and keratocystic odontogenic tumor (KOT); to correlate the MT with cellular proliferation; and to eval- uate the influence of the inflammation in MT. METHODS: Nine cases of radicular cyst (RC), nine den- tigerous cyst (DC), four orthokeratinized odontogenic cyst (OOC), and eight KOT were submitted to immu- nohistochemistry using anti-MT and anti-Ki-67. Indexes of MT (IMT) and Ki-67 (IK) were obtained. Lesions were grouped according to inflammation: mild-to-moderate (group A) and intense (group B). RESULTS: IMT proved to be highest in RC (91%), fol- lowed by DC (89%), KOT (78%), and OOC (63%). IMT was inversely correlated with IK in KOT, and OCC, but was positively correlated with RC and DC. No differences in IMT and in IK could be observed between groups A and B. CONCLUSIONS: The higher IMT found in RC and DC compared to OCC and KOT, as well as the differences between the last ones, is possibly correlated with their different histopathological features and clinical behavior. In RC and DC, MT may play a role in cellular prolifera- tion. However, it seems that MT is either less or is not related to proliferation in OOC and in KOT. Moreover, inflammation does not seem to alter IMT and IK. J Oral Pathol Med (2011) 40: 270–276 Keywords: keratocystic odontogenic tumor; Ki-67 Antigen; metallothionein; MIB-1 antibody; odontogenic cysts Introduction Odontogenic cysts are cavities lined by odontogenic- derived epithelium. Radicular (RC) and dentigerous cysts (DC) are the most prevalent odontogenic cysts and show a non-aggressive clinical behavior with rare recurrences (1). The term, odontogenic keratocyst, was re-classified as an odontogenic neoplasm and was renamed keratocystic odontogenic tumor (KOT) by the World Health Organization (WHO, 2005) (2). This change reflects KOT’s aggressive clinical behavior, high recurrence rate, destructive growth, and association with nevoid basal cell carcinoma syndrome (NBCCS) (2). In the same classification (2), orthokeratinized odontogenic cyst (OOC) was not considered a part of the spectrum of KOT, as it shows a less aggressive clinical behavior, lower proliferative activity, and low tendency to recur. After KOT reclassification, recent immunohistochemi- cal studies compared it with odontogenic cysts (3–7). In spite of their high prevalence, the pathogenesis and factors related to their biological behavior have yet to be fully elucidated. Metallothionein (MT) is a protein correlated with the homeostasis of essential metals, the regulation of cellu- lar differentiation and proliferation, and the inhibition of cellular apoptosis. These processes are involved not only in normal cellular behavior, but may also be reflected in the biological behavior of many lesions (8, 9). MT is immunodetectable in both myoepithelial and epithelial cells. Four isoforms can be identified: MT-I and MT-II isoforms are similar and can be observed in many tissues, such as the oral epithelium; MT-III is Correspondence: Aline Cristina Batista Rodrigues Johann, DDS, PhD, Professor, Clı´nica de Odontologia, Pontifı´cia Universidade Cato´lica do Parana´, Rua Imaculada Conceic¸a˜o, 1155, Prado Velho 80.215-901, Curitiba, PR, Brazil. Tel: +55 41 3271 2592, Fax: +55 41 3271 1405, E-mail: alinecristinabatista@yahoo.com.br Accepted for publication October 10, 2010 J Oral Pathol Med (2011) 40: 270–276 ª 2010 John Wiley & Sons A/S Æ All rights reserved wileyonlinelibrary.com/journal/jop doi: 10.1111/j.1600-0714.2010.00971.x Journal of Oral Pathology & Medicine