title: Exploration of the APC/beta-catenin (WNT) pathway and a histologic classification system for pulmonary artery intimal sarcoma. A study of 18 cases.
abstract: APC, a tumor suppressor gene in the Wnt pathway, stabilizes beta-catenin and controls cell growth. Mutation of APC or beta-catenin leads to nuclear accumulation of beta-catenin and transcription of cyclin D1/cyclin A. Pulmonary artery sarcoma (PAS) were studied by morphologic, immunohistochemical, and molecular genetic methods of the Wnt pathway. Eighteen cases were included: mean age 52 years, primary intraluminal location with typical clinical presentation. PAS were classified as epithelioid (n = 4) or malignant fibrous histiocytoma (MFH; spindled/pleomorphic, n = 4), myxofibrosarcoma (n = 8), and one each hemangiopericytoma-like or malignant inflammatory myofibroblastic tumor-like. The tumor cells demonstrated vimentin, focal actins, and rare focal desmin positivity. All but one were grade 2 or 3 by FNCLCC grading. Alteration in chromosome 5q21 (APC) was found in 4/14 PAS by LOH, mostly epithelioid-type; an MFH-type case demonstrated microsatellite instability (MSI) and nuclear beta-catenin. Cyclin D1 was expressed in seven tumors, all myxofibrosarcoma-type. No mutations were detected in APC or beta-catenin. In summary, PAS are predominantly intermediate grade myxofibrosarcoma in middle-aged males, and fatal in two-thirds of patients. Despite myofibroblastic phenotype, APC/beta-catenin pathway changes are rare. Cyclin D1, only expressed in the myxofibrosarcoma-type, is likely transcribed via factors other than beta-catenin.
authors.affiliation: Institute of Pathology, University of Regensburg, Franz-Josef Strauss Allee 11, D-93042, Regensburg, Germany. andreas.gaumann@klinik.uni-regensburg.de
authors.forename: A
authors.initials: A
authors.lastname: Gaumann
authors.forename: B
authors.initials: B
authors.lastname: Bode-Lesniewska
authors.forename: D R
authors.initials: DR
authors.lastname: Zimmermann
authors.forename: J C
authors.initials: JC
authors.lastname: Fanburg-Smith
authors.forename: C J
authors.initials: CJ
authors.lastname: Kirkpatrick
authors.forename: F
authors.initials: F
authors.lastname: Hofstädter
authors.forename: M
authors.initials: M
authors.lastname: Woenckhaus
authors.forename: R
authors.initials: R
authors.lastname: Stoehr
authors.forename: E C
authors.initials: EC
authors.lastname: Obermann
authors.forename: W
authors.initials: W
authors.lastname: Dietmaier
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D019925:Cyclin A / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D012509:Sarcoma / Q000145:classification* / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D019043:Vascular Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D019925:Cyclin A; D051176:beta Catenin; D019938:Cyclin D1