Introduction: Organ transplantation provides life-saving therapy for patients with end-organ disease. Tacrolimus is an immunosuppressive drug used to lower the risk of organ rejection. This study was performed to investigate the immunohistochemical expressions of Ki-67 (a proliferation associated antigen) and Bcl-2 (antiapoptotic protein) and their correlation with the increased risk of development of neoplasms in the buccal mucosa of tacrolimus-induced immunosuppressed albino rats.
Material & methods: Twenty adult male albino rats were divided into two equal groups. Group one treated with tacrolimus in a daily oral dose 0.5 mg/kg for 3 months. Group two served as negative control, received distilled water in comparable volume. Tissue samples were fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin and eosin to evaluate histopathological finding. Other sections were used to reveal the immunohistochemical expression of Ki-67 and Bcl-2 antibodies through computerized image j analysis software. The expression of both markers was analyzed statistically through using Mann-Whitney test.
Results: Histopathological finding showed moderate dysplasia in tacrolimus-treated group. There was marked increase in normal mitotic figures, basal cell hyperplasia, loss of basal cell polarity, swirling of the spinous layer, prominent nucleoli, hyperchromatism, and altered N/C ratio. Immunohistochemical finding revealed marked increase in the nuclear expression of Ki-67 in basal cells and cytoplasmic expression of Bcl-2 in all layers of keratinocytes in tacrolimus-treated group. Statistical finding in tacrolimus – treated group showed significant difference in the expression of Ki-67 and highly significant difference in the expression of Bcl-2.
Conclusion: There is an obvious relation between prolonged systemic use of tacrolimus and development of premalignant lesions. The marked increase in Ki-67 and Bcl-2 expression may play a role in tumorgenesis.