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Published on: January 14, 2014
Diffuse gliomas with FGFR3-TACC3 fusion have characteristic histopathological and molecular features
Franck Bielle1,2,3, Anna-Luisa Di Stefano3,4,5, David Meyronet6,7
1AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Service de Neuropathologie Raymond Escourolle, Paris, France.
Abstract:
Adult glioblastomas, IDH-wildtype represent a heterogeneous group of diseases. They are resistant to conventional treatment by concomitant radiochemotherapy and carry a dismal prognosis. The discovery of oncogenic gene fusions in these tumors has led to prospective targeted treatments, but identification of these rare alterations in practice is challenging. Here, we report a series of 30 adult diffuse gliomas with an in frame FGFR3-TACC3 oncogenic fusion (n = 27 WHO grade IV and n = 3 WHO grade II) as well as their histological and molecular features. We observed recurrent morphological features (monomorphous ovoid nuclei, nuclear palisading and thin parallel cytoplasmic processes, endocrinoid network of thin capillaries) associated with frequent microcalcifications and desmoplasia. We report a constant immunoreactivity for FGFR3, which is a valuable method for screening for the FGFR3-TACC3 fusion with 100% sensitivity and 92% specificity. We confirmed the associated molecular features (typical genetic alterations of glioblastoma, except the absence of EGFR amplification, and an increased frequency of CDK4 and MDM2 amplifications). FGFR3 immunopositivity is a valuable tool to identify gliomas that are likely to harbor the FGFR3-TACC3 fusion for inclusion in targeted therapeutic trials.
Insights
Adult gliomas with FGFR3-TACC3 fusions are aggressive and hard to treat. Constant FGFR3 staining is a reliable screening method for identifying these rare oncogenic fusions in patients for targeted therapies.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Genetics
Background:
- Adult glioblastomas, IDH-wildtype are aggressive brain tumors with poor prognosis.
- Conventional treatments offer limited efficacy for these heterogeneous diseases.
- Identifying rare oncogenic gene fusions is crucial for developing targeted therapies.
Purpose of the Study:
- To characterize the histological and molecular features of adult gliomas harboring the FGFR3-TACC3 fusion.
- To evaluate the utility of FGFR3 immunohistochemistry as a screening tool for this fusion.
- To identify potential therapeutic targets in these gliomas.
Main Methods:
- Histopathological analysis of 30 adult diffuse gliomas with FGFR3-TACC3 fusion.
- Immunohistochemistry for FGFR3 expression.
- Molecular analysis of genetic alterations, including EGFR, CDK4, and MDM2 amplifications.
Main Results:
- The study identified 27 WHO grade IV and 3 WHO grade II gliomas with FGFR3-TACC3 fusion.
- Recurrent morphological features included monomorphous ovoid nuclei, nuclear palisading, and thin parallel cytoplasmic processes.
- FGFR3 immunoreactivity demonstrated 100% sensitivity and 92% specificity for detecting the FGFR3-TACC3 fusion.
- Associated molecular features included typical glioblastoma alterations, absence of EGFR amplification, and increased CDK4/MDM2 amplifications.
Conclusions:
- FGFR3 immunopositivity is a valuable and sensitive method for screening gliomas with FGFR3-TACC3 fusion.
- This approach can facilitate the inclusion of appropriate patients in targeted therapeutic trials.
- Understanding these molecular features aids in personalized treatment strategies for aggressive gliomas.
