The expression of apoptotic proteins and matrix metalloproteinases in odontogenic myxomas

Purpose: The odontogenic myxoma is a rare benign tumor affecting the jaws. We hypothesize that odontogenic myxomas have dysregulated antiapoptotic mechanisms to assist in neoplastic growth. We believe that antiapoptotic proteins of the Bcl-2 family are over expressed and that tumor cells must generate some form of matrix proteinase. The aim of this study was to evaluate odontogenic myxomas for the expression of cell cycle protein Ki-67, apoptosis-regulating proteins Bcl-2, Bcl-XL, Bak, and Bax, and matrix metalloproteinases MMP-2, MMP-3, and MMP-9. Materials and Methods: Odontogenic myxomas submitted to oral pathology between 1974 and 1998 were evaluated. Twenty-six paraffin-embedded tissue sections were used in a standard immunohistochemistry protocol and incubated with one of the following antibodies: Bcl-2, Bcl-XL, Bak, Bax, or Ki-67. The sections were then incubated with anti-immunoglobulin conjugated to peroxidase-labeled dextran polymer in a Tris-HCl buffer. Counts of positive (staining) cells were completed in 5 high-power fields for each specimen. Each slide was reviewed by 2 investigators, and final data were pooled and averaged. Results: Specimen slides showed an increase in cells staining positively for anti-apoptotic proteins Bcl-2 and Bcl-X. An average of 6.5% of specimen cells were positive for Bcl-2 and 10.4% for Bcl-X. Control tissue showed only 1.1% of cells to be positive for Bcl-2 and 1.2% for Bcl-X. Less than 1% of both specimen and control cells stained positively for Ki-67. Proapoptotic proteins (Bak and Bax) were not detected, in tumor cells. Ninety percent of tumor cells stained positively for MMP-2 compared with 10% of controls. Specimen and controls were negative for MMP-3 and MMP-9. Conclusion: Odontogenic myxoma tumor cells did not show an increase in cell division. Less than 1% of tumor and control cells were positive for Ki-67. Odontogenic myxoma tumor cells showed increased expression of antiapoptotic proteins (Bcl-2 and Bcl-X) and the matrix metalloproteinase MMP-2. This study suggests that 2 mechanisms of disease progression used by the odontogenic myxoma are the production of antiapoptotic proteins and the secretion of matrix metalloproteinases. (C) 2003 American Association of Oral and Maxillofacial Surgeons.