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

• Published in: Virchows Archiv : an international journal of pathology 2008-11, Vol.453 (5), p.473-484
• Main Authors: Gaumann, A., Bode-Lesniewska, B., Zimmermann, D. R., Fanburg-Smith, J. C., Kirkpatrick, C. J., Hofstädter, F., Woenckhaus, M., Stoehr, R., Obermann, E. C., Dietmaier, W., Hartmann, A.
• Format: Article
• Language: English
• Subjects: Adenomatous Polyposis Coli Protein - genetics; Adenomatous Polyposis Coli Protein - metabolism; Adult; Aged; beta Catenin - genetics; beta Catenin - metabolism; Biological and medical sciences; Cyclin A - metabolism; Cyclin D1 - metabolism; Female; Humans; Investigative techniques, diagnostic techniques (general aspects); Loss of Heterozygosity - genetics; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Original Article; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pulmonary Artery - metabolism; Pulmonary Artery - pathology; Retrospective Studies; Sarcoma - classification; Sarcoma - genetics; Sarcoma - pathology; Sequence Analysis, DNA; Signal Transduction - physiology; Tunica Intima - metabolism; Tunica Intima - pathology; Vascular Neoplasms - classification; Vascular Neoplasms - genetics; Vascular Neoplasms - pathology
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-008-0671-0

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.