Desmoid tumor: a diseaseopportune for molecular insights
D. Kotiligam1, A.J.F. Lazar2, R.E. Pollock3 and D. Lev1
1Department of Cancer Biology and Sarcoma Research Centre, UT-MD Anderson Cancer Center, Houston, Texas, USA, 2Department of Pathology and Sarcoma Research Center, UT-MD Anderson Cancer Center, Houston, Texas, USA, 3Department of Surgical Oncology and Sarcoma Research Center, UT-MD Anderson Cancer Center, Houston, Texas, USA.
Offprint requests to: Dina Lev, Department of Cancer Biology and Sarcoma Research Center, UT-MD Anderson Cancer Center, 8515 Fannin St., Unit 1104, Houston, Texas 77054. USA. e-mail: dlev@mdanderson.org
Summary. Desmoid tumors are monoclonal proliferations that fall within a broad histologic spectrum of fibrous mesenchymal tumors that ranges from benign proliferations of scar tissue to high-grade fibrosarcomas. These low-grade tumors are extremely infiltrative locally, but lack the ability to metastasize systemically. While they are only rarely a direct cause of mortality, using current therapeutic modalities, these tumors have a high rate of local recurrence that can result in significant treatment related morbidity. Sporadic desmoids are usually associated with somatic mutations in codons 41 or 45 of exon 3 of ß-catenin (CTNNB1). Desmoid tumors occurring in the background of familial adenomatous polyposis (FAP) usually contain inactivating germline mutations in the adenomatous polyposis coli (APC) gene. CTNNB1 and APC are part of the Wnt signaling pathway and mutations in either gene result in stabilization of the ß-catenin protein and allow nuclear translocation and binding of ß-catenin to the T-cell factor/lymphoid enhancer factor (TCF/Lef) family of transcription factors, resulting in activation of target genes which may underlie desmoid tumor biology and clinical behavior. In an era of molecularly targeted therapeutics there is a real need to better grasp the molecular mechanisms behind desmoid tumorigenesis and progression. This knowledge will eventually result in the development of patient and tumor tailored therapies and assist in the control and eradication of this disease. Histol Histopathol 23, 117-126 (2007)
Key words: Desmoid, ß-catenin, APC, Estrogen receptors, c-Kit
DOI: 10.14670/HH-23.117