Signaling modification in Kaposi's sarcoma by sirolimus in a liver recipient: evidence of malignancy cured by immunosuppressant

[[abstract]]Sirolimus is one of the treatment modalities in organ transplant recipients with Kaposi’s sarcoma (KS) which involves abnormal dysregulation of Akt-mTOR signaling pathway. Signal modifi cations after sirolimus therapy in organ recipients with KS are unknown. The immunosuppressants were shifted from tacrolimus, MMF and prednisolone to sirolimus alone after the confi rmed diagnosis of KS in a liver recipient. Biopsies were performed before, two months, and 1 year after the start of sirolimus. VEGF, p-Akt, p-mTOR, and p-p70 S6 kinase were detected by immunohistochemitry and p-tuberin/TSC2 by Western blotting. Sequential expression changes of these signaling proteins were compared. Diseased skin, which was found to have KS after two-month treatment of sirolimus, was removed completely on the last biopsy and no residual KS was found pathologically. The patient went well without graft rejection. VEGF expression was suppressed thoroughly in two-month use of sirolimus. p-Akt, p-mTOR expression was decreased in two months, and disappeared in one year of treatment. p-p70 S6 kinase, expressed strongly in overlying epidermis initially, was suppressed completely in two-month and one-year treated specimens. p-tuberin/TSC2 was not detected in all the specimens, suggesting not a prominent event in this KS. In conclusion, sirolimus can cure KS in organ recipients without graft rejection. Long-term use of sirolimus has major effects on suppression of VEGF, p-Akt and p-mTOR in K