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. 2025:44:100964.
doi: 10.1016/j.ctarc.2025.100964. Epub 2025 Jul 14.

Fibroblast activation protein-expression in colorectal carcinomas and implications for clinical application

Meaghan Polack  1 , Gabi W van Pelt  1 , Augustinus S L P Crobach  2 , Lioe-Fee de Geus-Oei  3 , Rob A E M Tollenaar  1 , J Han J M van Krieken  4 , Wilma E Mesker  5
Affiliations
Free article

Fibroblast activation protein-expression in colorectal carcinomas and implications for clinical application

Meaghan Polack et al. Cancer Treat Res Commun. 2025.
Free article

Abstract

Background: Colorectal cancer is highly prevalent. The stromal tumour microenvironment significantly influences tumour behaviour, and cancer-associated fibroblasts (CAFs), as major component of tumour stroma, are increasingly studied. Specifically, CAF-marker fibroblast activation protein (FAP) is gaining interest as tracer for imaging using radiolabelled FAP-inhibitor (FAPI). We describe patterns of FAP-expression, and associations to intratumoural stroma amount, establishing a biological background and potential future reference to pathology assessment.

Materials and methods: Archival histological material from 125 stage-II/III CRC patients was collected. Haematoxylin-and-eosin staining was performed to determine the tumour-stroma ratio (TSR), indicating stromal percentages in primary tumours, lymph nodes (LNs) and biopsies. On immunohistochemistry stains, FAP-expression was semiquantitatively scored as little-no, heterogeneous, or moderate-high expression. Correlation of TSR and FAP-expression with Chi-square testing was assessed. Other patterns were also described, e.g. tumour epithelial FAP-expression.

Results: In total, 93 patients (40 stage-III colon [CC], 53 stage-II/III RC) were included. Correlation between 41 (44 %) stroma-high CRC (18/40 CC, 45 %; 23/53 RC, 43 %) with high FAP-expression was not significant (P = 0.428 CRC; P = 0.470 CC; P = 0.615 RC). The majority of CRC had any FAP-expression (78 CRC, 84 %), mostly the invasive front, and in most associated LN metastases (87 % CRC tumour-positive LN). However, FAP-expression was often heterogeneous, even staining healthy colon and lymphoid tissue.

Conclusions: CRCs and LN metastases generally express FAP, but levels vary significantly between and within tumours and have no direct correlation with TSR. Care has to be taken translating FAPI-PET/CT results with e.g. disease extent and activity, emphasizing the importance of multidisciplinary approach.

Keywords: Cancer-associated fibroblasts; Colorectal cancer; Fibroblast activation protein; Immunohistochemistry; Tumor-stroma ratio.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Wilma E. Mesker reports financial support was provided by Bollenstreekfonds, Hillegom, the Netherlands. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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