title: Extrarenal perivascular epithelioid cell tumors (PEComas) respond to mTOR inhibition: clinical and molecular correlates.
abstract: Perivascular epithelioid cell tumors (PEComas) are a group of rare mesenchymal tumors that typically show both melanocytic and smooth muscle cell features. Some types of PEComa are seen at high frequency in tuberous sclerosis complex (TSC). The TSC1 and TSC2 genes are commonly mutated in both TSC-associated and sporadic PEComas, and mTOR signaling pathway activation is also common in these tumors. Preliminary reports have indicated that the mTOR inhibitors sirolimus and related drugs have activity in some patients with non-TSC-associated PEComa. Here, we report on the use of these medications in the treatment of five consecutive patients with extrarenal nonpulmonary PEComas seen at one institution. Three complete responses, one partial response and one case of progression were seen. Molecular studies identified TSC2 aberrations in four of these patients, and TFE3 translocation was excluded in the resistant case. A review of all published cases as well as those reported here indicates that partial or complete response was seen in 6 of 11 PEComas, with 5 of 6 having a complete response. These findings highlight the consistent though incomplete activity of mTOR inhibitors in the treatment of PEComas.
authors.affiliation: Melanoma and Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. dicksonm@mskcc.org
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dickson
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schwartz
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: David J
authors.initials: DJ
authors.lastname: Kwiatkowski
authors.forename: Izabela A
authors.initials: IA
authors.lastname: Malinowska
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000068338:Everolimus; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D054973:Perivascular Epithelioid Cell Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012196:Review Literature as Topic; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus