From bench to bedside, blade, and back: FAP expression in juvenile angiofibroma. Potential implications for FAPI-PET/CT imaging and targeted therapy?

PURPOSE: Juvenile angiofibroma (JA) is a rare, benign fibrovascular tumor that predominantly affects adolescent males. The underlying biological mechanisms remain poorly understood. Fibroblast activation protein (FAP), known for its involvement in tumor invasion, matrix remodeling, and angiogenesis, has been implicated in various malignancies but has not been studied in JA so far. METHODS: We investigated FAP expression in JA samples (N = 19) using real-time (RT)-PCR (N = 10) and immunohistochemistry (N = 18). In addition, Vimentin and PECAM1/CD31 were analyzed to further characterize the tumor microenvironment. For one patient, preoperative FAPI-PET/CT imaging was conducted, and FAP expression was correlated with radiotracer uptake. Postoperative histopathological analyses of the excised tumor were performed to validate the imaging findings. RESULTS: We found consistent expression of FAP, Vimentin and PECAM1/CD31 in all JA analyzed by RT-PCR. Moreover, substantial intra-and intertumor heterogeneity in FAP protein expression was observed, ranging from negative up to strong positive areas. Vimentin and PECAM1/CD31 showed variable expression patterns consistent with the fibrovascular character of JA. FAPI-PET/CT imaging accurately identified the tumor, with radiotracer uptake closely matching the distribution of FAP expression observed histologically. CONCLUSIONS: This study is the first demonstrating FAP expression in JA and validating its occurrence using FAPI-PET/CT imaging. The strong correlation between FAP expression and radiotracer uptake in FAPI-PET/CT highlights the potential of this imaging modality as a non-invasive diagnostic tool. This will improve diagnosis and is the basis for further investigations of FAP-targeted therapies for JA treatment.