title: FAP-related desmoid tumors: a series of 44 patients evaluated in a cancer referral center.
abstract: Desmoid tumors (DTs), the commonest extra-intestinal manifestation of familial adenomatosis polyposis (FAP), are monoclonal neoplasms demonstrating fibroblastic - myofibroblastic differentiation; they are locally invasive without metastatic capacity. FAP-associated DT natural history knowledge is limited; we examined patient and tumor characteristics for a FAP-DT cohort and evaluated anti-DT therapy molecular target expression levels (immunohistochemical analyses, FAP-DT tissue microarray; TMA). Forty-four patients were classified as intra-abdominal (IA; n=26), abdominal wall (AW)/extra-abdominal (EA; n=12) or concomitant IA/AW (n=6) based on DT primary diagnosis location. Positive family histories were found in 62% of FAP versus 10% of DT patients. Surgery was the mainstay therapy for AW/EW patients, whereas IA DTs received surgery, chemotherapy, radiotherapy, tamoxifen, NSAIDs, and/or imatinib. Eight of 20 completely resected DTs in the IA and AW/EA groups recurred; 12 of 38 patients in these groups (33%) developed secondary lesions elsewhere. Two intestinal mesenteric DT patients died of disease, three from other cancers, 27 are alive with disease and 12 are alive without disease. All evaluable FAP-DT exhibited nuclear β-catenin, 65% were positive for cyclin D1, and 66% expressed nuclear p53. No ERα expression was observed, but ERβ was expressed in 72%. COX2 was expressed in all evaluable FAP-DTs. KIT was rarely found in DTs but both PDGFRs and their ligands were expressed. Comparing biomarker expression (IA vs. EA DTs), only nuclear ER-ß staining was significantly higher in EA lesions (p=0.0070); no other markers were site informative. Enhanced knowledge of FAP-DT molecular underpinnings will facilitate development of novel therapeutic strategies.
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Chiara
authors.initials: C
authors.lastname: Colombo
authors.forename: Wai Chin
authors.initials: WC
authors.lastname: Foo
authors.forename: David
authors.initials: D
authors.lastname: Whiting
authors.forename: Eric D
authors.initials: ED
authors.lastname: Young
authors.forename: Kristelle
authors.initials: K
authors.lastname: Lusby
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Pollock
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.forename: Dina
authors.initials: D
authors.lastname: Lev
mesh_terms: D000008:Abdominal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D011125:Adenomatous Polyposis Coli / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D015331:Cohort Studies; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D018222:Desmoid Tumors / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010982:Platelet-Derived Growth Factor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor