New markers for odontogenic lesions: role of the Nicotinamide N-methyltransferase

• ¹ Polytechnical University of Marche, Department of Clinical Specialistic and Dental Sciences, Italy
• ² University of Foggia, Department of clinical and experimental medicine, Italy

Aim. Odontogenic tumours constitute a group of heterogeneous diseases, which mostly consist of benign neoplasms, but some types show local aggressiveness and a high rate of recurrences, requiring extensive bone resection. Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme which catalyzes the N-methylation of nicotinamide and other compounds, playing an important role in controlling the intracellular concentration of nicotinamide. Growing evidence shows that NNMT protein levels are high in several human cancers, and increased NNMT expression has been linked to tumour aggressiveness. In the light of current knowledge, we can deduce that NNMT can support carcinogenesis and be valid both as a potential molecular target in anticancer therapies and as an early diagnostic and/or prognostic marker in oncology. Therefore, in this research project, immunohistochemical analyses were performed in order to evaluate, for the first time, the validity of NNMT as a tumour marker for odontogenic lesions, both tumoral and not tumoral, by verifying the enzyme positivity on ameloblastoma and odontogenic keratocyst samples. Materials and Methods. This study included 40 surgical specimens obtained from 23 patients: 11 with a diagnosis of ameloblastoma (distinguished in the central, unicystic and peripheral subtypes) and 12 diagnosed with odontogenic keratocyst (syndromic and not syndromic). 4-μm serial sections from formalin-fixed, paraffin embedded blocks were cut for each case and mounted on poly-L-lysine-coated glass slides. The specimens were incubated overnight at 4°C with polyclonal rabbit anti-NNMT antibodies at dilution 1:500 with PBS 1X. Immunohistochemical staining was evaluated both in the epithelial and stromal cells, at the nuclear and cytoplasmic levels. NNMT expression was evaluated through the quantification of the extension and the intensity of coloring. Results. In ameloblastomas and odontogenic keratocysts, no significant difference emerged from the comparison between the expression of NNMT and the clinical-pathological features. On the other hand, the comparison between primitive and recurrent odontogenic keratocysts is interesting, as in the stromal cells a statistically significant difference was highlighted both at the nuclear and cytoplasmic levels: the primitive cases showed a greater expression of NNMT compared to the recurrences. This may be the direct consequence of a different metabolic activity of the tissues taken into consideration. Afterwards, it was observed that cases of primitive ameloblastoma expressing low cytoplasmic epithelial NNMT levels have a significantly longer disease-free survival than cases with high levels of enzyme (times medians: 75 vs 15 months). Conversely, in odontogenic keratocysts there is no significant difference between lesions with low NNMT expression and those with high levels of NNMT. Discussion. Although no statistically significant differences emerged from the comparison of lesions in various aspects, the results of this research work are still promising. The lack of correlations could be mainly attributed to the small number of cases taken into consideration. Further studies on larger series could reveal a prognostic utility of NNMT also for some types of odontogenic lesions.