Ming Zhong, DDS, MS, Jie Wang, DDS, MD, and Yangli Yue, DDS
Department of Pathology, College of Stomatology, China Medical University, Shenyang, P. R. China
Purpose: To investigate the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human ameloblastoma (AB), and to explore the relationship of the three factors with AB’s biological behavior in combination with clinicopathological characteristics.
Materials and Methods: Specimens of 43 cases of AB, 10 cases of odontogenic keratocyst (OKC), and 16 cases of normal oral mucosa were examined immunohistochemically using the streptavidin-biotin method to determine the expression of MMP-2, MMP-9 and TIMP-1.
Results: Of the 16 cases of normal oral epithelia, MMP-2 was positively expressed in six cases. In the 10 OKC cases, MMP-2 expression was strongly positive in stratum spinosum in two cases and weak or lost in stratum basale. MMP-2 was strongly expressed in the central and peripheral cells of the tumor islands in 28 cases of AB. There was a significant difference among these three groups (p<0.01). MMP-9 expression was negative in all cases of normal oral mucosa, and extensively positive in the entire strata of peritumor epithelia in five cases of AB. MMP-9 was strongly expressed in two of nine cases of OKC. MMP-9 was strongly expressed in the central and peripheral cells of the tumor islands in 30 cases of AB. There was no difference between normal epithelia and OKC (p>0.05). There was a great difference between AB and normal oral mucosa (p<0.01). The positive rate and intensity increased as AB recurred and transformed malignantly, but the increases were not associated with age, sex, pathological type, or disease location. MMP-2 and MMP-9 were positively expressed in fibroblasts, endothelial cells, and inflammatory cells including monocytes, neutrophils, plasmacytes and lymphocytes. TIMP-1 was weakly or not expressed in normal oral mucosa, OKC and AB.
Conclusion: The high expression of MMP-2 and MMP-9 is related to the biological behavior of AB. Imbalance in the expression of MMP-2 and MMP-9 proteins is one mechanism for the invasiveness of AB. The MMPs activation produced by stromal cells is also related to the invasiveness of AB.
(Int Chin J Dent 2004; 4: 19-26.)
Clinical Significance: The study provided that activity of MMP-2 and MMP-9 was closely related to the clinico-biological behavior of AB, which provided a new target to therapy for AB by gene.
Key Words: ameloblastoma, immunohistochemistry, matrix metalloproteinase, odontogenic keratocyst.