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Cohen SJ , Alpaugh RK , Palazzo I , Meropol NJ , Rogatko A , Xu Z , Hoffman JP , Weiner LM , Cheng JD
Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma
Pancreas. 2008 Aug;37(2) :154-8
AbstractOBJECTIVES: Given the extensive desmoplastic response associated with pancreatic adenocarcinoma, we hypothesized that the stromal protein fibroblast activation protein (FAP) would be highly expressed and associated with the presence of fibrosis and other clinical features. METHODS: Paraffin-embedded pancreatic adenocarcinomas that were resected with curative intent from 1992 to 2003 were used for this study. Fibroblast activation protein expression by immunohistochemical analysis was evaluated both by intensity (0-3+) and percentage. Fibrosis was estimated as a percentage of each tumor specimen. RESULTS: Ninety percent (63/70) of specimens demonstrated FAP expression. Expression was significantly more pronounced in tumor-associated myofibroblasts immediately adjacent to tumor than in surrounding tumor-associated myofibroblasts (P < 0.001). Lower FAP expression in adjacent tumor-associated myofibroblasts was associated with increased fibrosis (P = 0.02). Greater FAP expression in surrounding tumor-associated myofibroblasts was associated with an increased chance of having positive lymph nodes for all patients (P = 0.03) and a higher risk of tumor recurrence (P = 0.015) and death (P = 0.02) for patients who did not receive preoperative therapy. CONCLUSIONS: Fibroblast activation protein is highly expressed in pancreatic adenocarcinoma, with greatest expression immediately adjacent to tumor. Higher FAP expression is associated with worse clinical outcome. The investigation of FAP inhibitors as a therapeutic strategy against pancreatic cancer should be considered.
NotesCohen, Steven J Alpaugh, R Katherine Palazzo, Irma Meropol, Neal J Rogatko, Andre Xu, Zhiheng Hoffman, John P Weiner, Louis M Cheng, Jonathan D P30 CA006927/CA/United States NCI Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Pancreas Pancreas. 2008 Aug;37(2):154-8.