Expression of fibroblast activation protein and the clinicopathological relevance in distal cholangiocarcinoma

Abstract

Objectives: The current survival of patients with distal cholangiocarcinoma (dCCA) is poor. There is a need to develop new prognostic and predictive biomarkers to improve the survival of patients. Fibroblast activation protein (FAP) expression has been associated with survival in several solid malignancies. The goal of this study was to evaluate the expression pattern and prognostic significance of FAP in dCCA.

Materials and methods: FAP expression was examined in 57 resected dCCA specimens and 28 paired lymph node metastasis specimens, as well as 10 benign bile ducts using immunohistochemistry. FAP expression was scored in the epithelial and stromal component of the dCCA specimens. The association between FAP expression and prognosis was evaluated using univariable and multivariable statistical modeling.

Results: FAP expression was absent in the benign controls. FAP expression was evident in the epithelial 43 (75%) and stromal compartment 34 (60%) of dCCA. There was no association between epithelial or stromal FAP expression and clinicopathological factors. Epithelial FAP expression (HR 0.4 95% CI 0.20–0.78; p=.007) but not stromal FAP expression was significantly associated with better survival in univariable and multivariable analysis.

Conclusions: FAP overexpression is evident in dCCA. There was a positive association between epithelial FAP expression and better survival which merits further evaluation.

Keywords:

• Distal cholangiocarcinoma
• fibroblast activation protein
• immunohistochemistry
• microenvironment
• survival

Author contributions

JB, RA and BA conceived and designed the study. KSH performed immunohistochemical staining. AS performed clinicopathological evaluation and evaluation of immunohistochemical staining. JB, JN and BA performed the statistical analysis. JB, BA and JN analyzed and interpreted the data and revised the manuscript. RA, KSH, AS and JN performed critical revision of the manuscript. All authors approved the final version for publication.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research work was supported by Government grant for clinical research (http://www.skane.se/fou/alf).