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.