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.
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Acknowledgements
The authors wish to acknowledge the excellent technical support of Martina Waeber, Steffi Götz, Anja Vilberth, and Anne Pietryga-Krieger performing immunohistochemistry, LOH, and sequence analysis. We also thank Prof. E. Geissler for critical reading of the manuscript.
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Gaumann, A., Bode-Lesniewska, B., Zimmermann, D.R. et al. Exploration of the APC/β-catenin (WNT) pathway and a histologic classification system for pulmonary artery intimal sarcoma. A study of 18 cases. Virchows Arch 453, 473–484 (2008). https://doi.org/10.1007/s00428-008-0671-0
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DOI: https://doi.org/10.1007/s00428-008-0671-0