The Role of Fibroblast Activation Protein in Glioblastoma and Gliosarcoma: A Comparison of Tissue,68Ga-FAPI-46 PET Data, and Survival Data

胶质肉瘤 免疫组织化学 成纤维细胞活化蛋白 胶质母细胞瘤 病理 医学 癌症研究 成纤维细胞 癌症 生物 内科学 细胞培养 遗传学
作者
Christoph Oster,Lukas Kessler,Tobias Blau,Kathy Keyvani,Kim M. Pabst,Wolfgang P. Fendler,Pedro Fragoso Costa,Lazaros Lazaridis,Teresa Schmidt,Jonas Feldheim,Daniela Pierscianek,Hans‐Ulrich Schildhaus,Ulrich Sure,Yahya Ahmadipour,Christoph Kleinschnitz,Nika Guberina,Martin Stuschke,Cornelius Deuschl,Björn Scheffler,Ken Herrmann,Sied Kebir,Martin Glas
出处
期刊:The Journal of Nuclear Medicine [Society of Nuclear Medicine]
卷期号:65 (8): 1217-1223
标识
DOI:10.2967/jnumed.123.267151
摘要

Despite their unique histologic 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 plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68Ga–FAP inhibitor (FAPI)–46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0–3, with higher values indicating stronger expression). Additionally, 68Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue (P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUVmean and SUVpeak of 68Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUVmean and SUVpeak in 68Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis.
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