(1) Faculty of Dentistry, Mansoura University, Mansoura, Egypt
(2) Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Gingival overgrowth is one of several oral side effects of cyclosporine A, a potent immunosuppressant drug, which is commonly used to prevent organ transplant rejection. Disturbances of proliferation and apoptosis are fundamental events in early carcinogenesis, and may be useful in characterizing tissue that is histologically normal but at high-risk for neoplastic growth. Thus, it would be valuable to investigate the immunohistochemical expressions of Ki-67 (a proliferation associated antigen) and Bcl-2 (antiapoptotic protein) and their potential role in the pathogenesis of cyclosporine A induced gingival hyperplasia (CIGH) and assessment of their levels of expression in keratinocytes and underlying connective tissue. This study was carried out in an attempt to evaluate the potential roles of BCL-2 and Ki67 in the pathogenesis of CIGH and their correlation with the increased risk of development of neoplasms in gingival tissues of CIGH.
Materials and methods
This study involves gingival biopsies collected from renal transplanted patients receiving cyclosporine-A with moderate to severe gingival overgrowth during gingivectomy procedures. Normal healthy tissue samples without clinical signs of periodontal inflammation were also included as control samples. Tissue samples were fixed in 10% formalin, embedded in paraffin and stained with hematoxylin and eosin to evaluate the histopathologic presentation of gingival enlargement. Sections were incubated separately with Bcl-2 and Ki-67 monoclonal antibodies. Computerized image analysis software was used to count the number of immunopositive cells regardless of intensity as well as the number of the remaining unstained ones. Ki-67 and Bcl-2 labeling indices were statistically analyzed.
The expression patterns of Ki-67 and Bcl2 were significantly higher (p ˂ 0.000) in both epithelium and connective tissues of cyclosporine-A treated groups as compared to normal healthy tissues. Statistically significant positive correlations were found between the number of Ki-67 positive cells and Bcl-2 positive cells in each group.
In conclusion increased expression of Bcl-2 and Ki-67 may have a role in the pathogenesis of gingival overgrowth induced by cyclosporine-A and patients with CIGH are at high risk of development of neoplasms.