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

Virchows Arch. 2008 Nov;453(5):473-84. doi: 10.1007/s00428-008-0671-0. Epub 2008 Sep 20.


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.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Adult
  • Aged
  • Cyclin A / metabolism
  • Cyclin D1 / metabolism
  • Female
  • Humans
  • Loss of Heterozygosity / genetics
  • Male
  • Middle Aged
  • 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
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Adenomatous Polyposis Coli Protein
  • Cyclin A
  • beta Catenin
  • Cyclin D1