OS08.5.A THE ROLE OF FIBROBLAST ACTIVATION PROTEIN IN GLIOBLASTOMA AND GLIOSARCOMA - A COMPARISON OF TISSUE, 68GA-FAPI-46 POSITRON EMISSION TOMOGRAPHY AND SURVIVAL DATA
Authors: Oster C , Kessler L , Blau T , Keyvani K , Pabst K , Fendler W , Fragoso Costa P , Lazaridis L , Schmidt T , Feldheim J , Pierscianek D , Schildhaus H , Sure U , Ahmadipour Y , Kleinschnitz C , Guberina N , Stuschke M , Deuschl C , Scheffler B , Herrmann K , Kebir S , Glas M 
Published: October 2024

Abstract

BACKGROUND
Despite their unique histological features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast-activation-protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that play a critical role in tumor growth and invasion. Few case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma, possibly for its predominant mesenchymal differentiation. However, the prognostic impact of FAP in glioblastoma and gliosarcoma is unclear.

METHODS
In a retrospective analysis, patients diagnosed with glioblastoma without sarcomatous differentiation and gliosarcoma were enrolled. Histological examination was performed using immunohistochemical FAP-staining and quantitative analysis with a standardized FAP score (0 to 3, with higher values indicating stronger expression). In a subset of patients, FAPI46-PET has been performed. The SUV values are planned to be correlated with FAP-expression in the tumor tissue. Data obtained from immunohistochemical analysis and SUV values are planned to be brought into perspective with clinically relevant prognostic factors, including survival estimates.

RESULTS
We enrolled 61 patients, including 13 diagnosed with gliosarcoma. Our analysis revealed that gliosarcomas exhibit significantly higher FAP expression (median FAP score: 3) compared to glioblastomas without sarcomatous differentiation (median FAP score: 0.5, p&lt;0.0001), where FAP was predominantly observed in the perivascular space. In gliosarcomas, FAP was also expressed by neoplastic cells. Moreover, a significant relationship was established between the immunohistochemical FAP scores and the SUVmean and SUVpeak values on PET, suggesting that the PET tracer uptake accurately reflects the tumor’s FAP expression. However, the differential expression of FAP suggests its potential as both a diagnostic marker in 68Ga-FAPI-46 PET and a therapeutic target. This hypothesis is further supported by the application of 68Ga-FAPI-46 PET in a 66-year-old female patient with recurrent gliosarcoma, alongside immunohistochemical analysis of tumor tissue. Both methods identified elevated FAP expression and uptake, underscoring the feasibility of FAP as a target for nuclear medicine therapies in brain tumors.

CONCLUSIONS
Our study establishes a significant correlation between SUVmean/SUVpeak in 68Ga-FAPI-46 PET scans and FAP expression in glioblastoma. Gliosarcomas express significantly more FAP than other glioblastomas. These insights suggest FAP’s potential as a theranostic target. We plan to investigate the effectiveness of FAP-specific tracers in treating recurrent gliosarcoma, aiming to open new therapeutic avenues.