Exploration of the APC/β-catenin (WNT) pathway and a histologic classification system for pulmonary artery intimal sarcoma. A study of 18 cases

A. Gaumann, B. Bode-Lesniewska, D. R. Zimmermann, Julie Fanburg-Smith, C. J. Kirkpatrick, F. Hofstädter, M. Woenckhaus, R. Stoehr, E. C. Obermann, W. Dietmaier, A. Hartmann

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Abstract

APC, a tumor suppressor gene in the Wnt pathway, stabilizes β-catenin and controls cell growth. Mutation of APC or β-catenin leads to nuclear accumulation of β-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 β-catenin. Cyclin D1 was expressed in seven tumors, all myxofibrosarcoma-type. No mutations were detected in APC or β-catenin. In summary, PAS are predominantly intermediate grade myxofibrosarcoma in middle-aged males, and fatal in two-thirds of patients. Despite myofibroblastic phenotype, APC/β-catenin pathway changes are rare. Cyclin D1, only expressed in the myxofibrosarcoma-type, is likely transcribed via factors other than β-catenin.

Original languageEnglish (US)
Pages (from-to)473-484
Number of pages12
JournalVirchows Archiv
Volume453
Issue number5
DOIs
Publication statusPublished - Nov 1 2008

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All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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