Prostaglandins Cell Culture Pcr CYCLOOXYGENASE-TWO REGULATES PROLIFERATION IN AGGRESSIVE FIBROMATOSIS (DESMOID TUMOR)

Introduction: Aggressive fibromatosis (desmoid tumor) is a locally invasive soft tissue lesion, composed of a monoclonal proliferation of benignappearing spindle (fibroblast like) cells. A subset of lesions contain a somatic mutation in the adenomatous polyposis coli (APC) gene (1). Familial Adenomatosis Polyposis (FAP) is an inherited pre-neoplastic condition that predisposes to colonic neoplasia and occasional fibromatoses, that is caused by a germ-line mutation in the APC gene. A large percentage of sporadic colonic polyps and cancers also harbor somatic APC mutations. Cyclooxygenases (COX) are enzymes involved in prostaglandin synthesis. COX-1 is ubiquitously expressed, and plays a role in normal physiology, while COX-2 is expressed in only select sites, usually by cells that are involved in an inflammatory or proliferative process. Normal fibroblasts do not express COX-2 (2). Colonic neoplasms express COX-2 and in mouse model of FAP, COX-2 blockade significantly decreases the number of colon tumours formed (3). Current treatments for aggressive fibromatosis are less than satisfactory, with high recurrence rates, loss of function, or local complications being not uncommon outcomes (4). A pharmacological agent to retard tumor growth would be a useful in this lesion. COX-2 blockade is one such potential treatment. The purpose of this study is to determine if aggressive fibromatosis expresses COX-2, and if COX-2 blockade in-vitro will alter cellular proliferation or apoptosis rates.