ABSTRACT
A 19-year old patient with tuberous sclerosis presented with a renal angiomyolipoma. Because animal trials of tuberous sclerosis showed an effect of rapamycin on renal tumors, our patient was administered rapamycin for 6 months. During this time, the renal angiomyolipoma shrank significantly, regrew during an 8-month period, and decreased in size again after readministration of rapamycin.
Subject(s)
Angiomyolipoma/drug therapy , Antibiotics, Antineoplastic/therapeutic use , Kidney Neoplasms/drug therapy , Sirolimus/therapeutic use , Tuberous Sclerosis/complications , Adult , Angiomyolipoma/etiology , Humans , Kidney Neoplasms/etiology , Male , Treatment OutcomeABSTRACT
BACKGROUND: Angiofibromas occur sporadically, and they develop in most patients with tuberous sclerosis complex (TSC), which is associated with alterations of the tumor suppressor genes TSC1 or TSC2. Loss of tuberin, the protein product of TSC2, has been shown in the interstitial fibroblast compartment of TSC-associated angiofibromas. It is unclear whether there is also a loss of hamartin, the product of TSC1 in TSC-associated and sporadic angiofibromas. METHODS: The expression of hamartin and tuberin was analyzed by immunohistochemistry in 59 TSC-associated and 12 sporadic angiofibromas using affinity-purified antibodies. RESULTS: Loss of expression of both tuberin and hamartin was detected in 14 angiofibromas, loss of only tuberin in three, and loss of only hamartin in four TSC-associated angiofibromas; but there was no loss in the sporadic angiofibromas. Only the interstitial cells, but not the vascular cells, showed a loss of expression of tuberin or hamartin. CONCLUSIONS: Loss of tuberin or hamartin occurred in a minority of the TSC-linked angiofibromas, but not in the sporadic angiofibromas. The absence of both tuberin and hamartin in some of the tumors suggests that the stability of tuberin and hamartin, which are believed to form an active complex in vivo, is negatively affected by the absence of either of the partners.
