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From bench to bedside, blade, and back: FAP expression in juvenile angiofibroma. Potential implications for
Lukas Pillong1, Caroline Burgard2, Florian Rosar2
1Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University, 66421, Homburg, Germany. lukas.pillong@uks.eu.
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.
Insights
Fibroblast activation protein (FAP) is expressed in juvenile angiofibroma (JA), a rare tumor. FAPI-PET/CT imaging accurately detects FAP, showing potential for improved JA diagnosis and targeted therapy development.
Area of Science:
- Oncology
- Molecular Biology
- Medical Imaging
Background:
- Juvenile angiofibroma (JA) is a rare, benign fibrovascular tumor affecting adolescent males.
- The biological mechanisms underlying JA are poorly understood.
- Fibroblast activation protein (FAP) is involved in tumor progression but unstudied in JA.
Purpose of the Study:
- To investigate FAP expression in JA.
- To characterize the tumor microenvironment using Vimentin and PECAM1/CD31.
- To evaluate FAPI-PET/CT imaging for JA diagnosis.
Main Methods:
- Real-time PCR and immunohistochemistry analyzed FAP, Vimentin, and PECAM1/CD31 in JA samples.
- FAPI-PET/CT imaging was performed preoperatively in one patient.
- Histopathological analysis validated imaging findings.
Main Results:
- Consistent FAP, Vimentin, and PECAM1/CD31 expression found in all JA samples.
- Significant heterogeneity in FAP protein expression observed.
- FAPI-PET/CT accurately identified the tumor, correlating with FAP distribution.
Conclusions:
- This is the first study demonstrating FAP expression in JA.
- FAPI-PET/CT imaging shows potential as a non-invasive diagnostic tool for JA.
- Findings support further research into FAP-targeted therapies for JA.
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