FAP-related desmoid tumors: a series of 44 patients evaluated in a cancer referral center
Chiara Colombo1,2*, Wai Chin Foo3*, David Whiting1,2, Eric D. Young1,2, Kristelle Lusby1,2, Raphael E. Pollock1,2, Alexander J. Lazar2,3 and Dina Lev2,4
Departments of 1Surgical Oncology, 3Pathology, 4Cancer Biology and the 2Sarcoma Research Center at the University of Texas MD Anderson Cancer Center, Houston, Texas, USA
*These authors made equal contributions to the manuscript.
Offprint requests to: Dina Lev, MD, Department of Cancer Biology, M.D. Anderson Cancer Center, 8515 Fannin, Unit 1104, Houston TX 77054, USA. e-mail: firstname.lastname@example.org
Summary. 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 ß-catenin, 65% were positive for cyclin D1, and 66% expressed nuclear p53. No ERα expression was observed, but ERß 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. Histol Histopathol 27, 641-649 (2012)
Key words: Gardner syndrome, Desmoid tumors, APC, ß-catenin, Targeted therapy