title: High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis.
abstract: An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07-2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13-3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.
authors: Department of Medical Biosciences, Pathology, Umeå University, Umea, SE-901 85, Sweden. maria.wikberg@medbio.umu.se
authors: Maria L
authors: ML
authors: Wikberg
authors: Sofia
authors: S
authors: Edin
authors: Ida V
authors: IV
authors: Lundberg
authors: Bethany
authors: B
authors: Van Guelpen
authors: Anna M
authors: AM
authors: Dahlin
authors: Jörgen
authors: J
authors: Rutegård
authors: Roger
authors: R
authors: Stenling
authors: Ake
authors: A
authors: Oberg
authors: Richard
authors: R
authors: Palmqvist
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D010450:Endopeptidases; D005260:Female; D005500:Follow-Up Studies; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D053842:Microsatellite Instability; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha