The expression of Fibroblast Activation Protein in human colon carcinoma

Abstract

9668 Background: Human Fibroblast Activation Protein (FAP)/seprase is a 97-kd surface glycoprotein with dipeptidyl peptidase and gelatinolytic activity expressed on tumor associated fibroblasts in the majority of epithelial cancers including colon adenocarcinomas. FAP overexpression has been shown to promote tumor growth in animal models, and clinical trials targeting FAP enzymatic activity have been initiated. The primary objective of this study was to evaluate expression levels of FAP in human colon cancers by immunohistochemisty and relate its expression to clinical outcome. Methods: Sections of paraffin-embedded resected primary human colon cancer specimens from 1996 through 2001 within the Fox Chase Cancer Center tumor bank were stained with D8 antibody directed against FAP/seprase. Grading of staining was performed by assessment of FAP staining intensity (none, light, medium, dark) and overall percent of stromal staining (0, 1–10%, 11–50%, 51%+) as previously established. Survival time and time to recurrence data were analyzed using Kaplan-Meier plots, log-rank tests and Cox proportional hazards models. Results: 138 patients with resected specimens were available for study (mean follow-up 1050 days) with 6 patients (4%) stage I, 52 (38%) stage II, 43 (31%) stage III, and 37 (27%) stage IV. FAP was detected in over 93% of specimens and semiquantitative staining was scored as 1+ in 28 (20%), 2+ in 52 (38%) and 3+ in 49 (35%). FAP staining was graded as light in 45 (33%), medium in 48 (35%), and dark in 36 (26%). Overall survival was higher in patients with medium or dark staining intensity (median days not yet achieved) versus those with no or light staining intensity (median = 1415 days, p= .02). However, the impact of FAP intensity on overall survival was lost when analyzed with stage within a multivariate model. Thus, FAP staining intensity correlated inversely with stage. Conclusion: Patients whose colon cancers intensely express FAP are more likely to have early stage disease. This suggests that clinical trials utilizing FAP as a therapeutic target to disrupt FAP-driven tumor growth may have greater potential efficacy prior to the establishment of metastatic disease. No significant financial relationships to disclose.