Discoidin domain receptors: a promoter of the aggressive behavior of ameloblastomas

Discoidin domain receptors 1 and 2 (DDR1 and DDR2) are members of the receptor tyrosine kinases, which regulate fundamental cellular processes concerning proliferation, differentiation, adhesion, motility, and apoptosis. The dysregulation of these receptors is linked to a number of human diseases, including fibrotic disorders, atherosclerosis, and cancer. However, there have been no studies that analyzed the expression of these DDRs in ameloblastomas (ABs). In this study, we investigated the expression level and distribution of both DDRs in ABs and determined whether these receptors could predict the prognosis of the disease. Real-time reverse transcription polymerase chain reaction, western blot, and immunohistochemical analyses were performed to detect the DDR mRNA and protein expression levels in normal oral mucosa (NOM) and ABs. The relationship of the DDRs with the clinicopathology and prognosis of ABs was analyzed statistically. The mRNA expression levels of DDR1 and DDR2 were found to be increased by 3.42- and 3.66-fold in ABs versus NOM, respectively. Recurrent ABs displayed higher DDR mRNA expression than did primary ABs (P < 0.05). Using western blot analysis, the DDR proteins were found to be lower in NOM than in ABs (P < 0.05), and primary ABs showed lower expression levels than did recurrent ones (P < 0.05). Immunohistochemically, the DDR protein expressions were markedly higher in ABs than in NOM (P < 0.05), and AB patients with higher DDR protein expression showed higher recurrence (P < 0.05). Multivariate analysis with the Cox proportional hazards model indicated the expression of both DDRs to be an independent prognostic factor of ABs. It was suggested that the up-regulation of DDR expression might play an important role in the tumorigenesis and aggressiveness of ABs. Thus, DDR protein expression may be considered as a good biomarker for indicating the prognosis of ABs.