Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma.
OBJECTIVE
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.
Cohen
Steven J
SJ
Department of Medical Oncology, Fox Chase Cancer Center, Jeanes Hospital, Philadelphia, PA 19111-2497, USA. S_Cohen@fccc.edu
Alpaugh
R Katherine
RK
Palazzo
Irma
I
Meropol
Neal J
NJ
Rogatko
André
A
Xu
Zhiheng
Z
Hoffman
John P
JP
Weiner
Louis M
LM
Cheng
Jonathan D
JD
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D010450:Endopeptidases; D005260:Female; D005355:Fibrosis; D018093:Gelatinases; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D012008:Recurrence; D012697:Serine Endopeptidases / Q000378:metabolism*; D015996:Survival Rate; D000099167:Fibroblast Activation Protein Alpha
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha