Desmoid-type fibromatosis (DTF) are locally aggressive benign clonal fibroblastic/myofibroblastic proliferations that are defined by infiltrative growth in deep soft tissue have an increased propensity for local recurrence but no metastatic potential. They are known to be related to perturbation in the APC/beta-catenin/Wnt-signaling pathway and are characterized by demonstration of frequent beta-catenin nuclear localization on immunohistochemistry. The majority of cases occur sporadically while rare cases arise infrequently as part of a familial syndrome (called familial adenomatous polyposis) due to germline mutation in the adenomatous polyposis gene (APC). There are 3 types of DTF based on anatomic distribution: 1. Intra-abdominal (mesenteric) fibromatosis; 2. Abdominal fibromatosis; 3. Extra-abdominal fibromatosis. These tumors are morphologically identical and essentially indistinguishable from each other. More so, the biology of these tumors is unpredictable and consistent reproducible predictive biomarkers in terms of response to therapy are lacking. Emerging data from recent large clinical studies and molecular profiling seems to indicate significant heterogeneity in tumor biology among the different types of DTF. Specifically, desmoid tumors with CTNNB1 41A gene mutation have been found to be associated with a better statistically significant 5-year recurrence free survival compared to those with S45F mutation and desmoids of abdominal site behave less aggressively than those in extra-abdominal sites. Indeed, the largest prospective outcome data on DTF from the French Sarcoma Group, suggests that anatomic location is the single most important determinant of event free survival.
In spite of the recent strides in the biology of DF, the optimal treatment remains a challenge with an unacceptably high recurrence rate with various multi-modality approaches including surgery, chemoradiation, anti-estrogenic and different molecular targeted therapies. There is thus an urgent need for thorough understanding of the molecular biology of DTF with the ultimate goal of developing better treatment strategies. There is paucity of data in the proteomic analysis of desmoid tumors. Using a novel quantitative mass spectrometry based proteomics platform, we propose to elucidate any differences in protein signatures between the different types of desmoid type fibromatosis.
LAY VERSION OF ABSTRACT- “Quantitative Proteomics Analysis of Desmoid-Type Fibromatosis.”
