AB055. FGFR1 amplification in thymic epithelial tumors (TETs): a study from 48 cases
Original Research

AB055. FGFR1 amplification in thymic epithelial tumors (TETs): a study from 48 cases

Véronique Hofman1, Lara Chalabreysse2, Jean-Philippe Dales3, Romain Dubois4, Audrey Mansuet-Lupo5, Anne de Muret6, Nicolas Piton7, Isabelle Rouquette8, Véronique Secq9, Damien Sizaret6, Vincent Thomas de Montpréville10, Alice Millière11, Salomé Lalvé1, Pascale Missy12, Clémentine Lemattre12, Jonathan Benzaquen13, Paul Hofman1, Nicolas Girard14, Álvaro López-Gutiérrez15, Benjamin Besse15, Thierry Jo Molina16

1IHU RespirERA, Laboratory of Clinical and Experimental Pathology, Nice Hospital, University Côte d'Azur, Nice, France; 2Department of Pathology, Louis-Pradel Hospital, Lyon, France; 3Department of Pathology, Nord, AP-HM Hospital, Marseille, France; 4Department of Pathology, University Hospital of Lille, Lille, France; 5Department of Pathology, Cochin Hospital, Université Paris Cité, Paris, France; 6Department of Pathology, Tours University Hospital, Tours, France; 7Department of Pathology, Rouen University Hospital, Rouen, France; 8Department of Pathology XPATH des Côteaux, Toulouse, France; 9Department of Pathology, Félix Guyon Hospital in Saint-Denis, La Réunion, France; 10Department of Pathology, Marie Lannelongue Hospital, Le Plessis-Robinson, France; 11Department of Pathology, Dijon Hospital, Bourgogne, France; 12French Cooperative Thoracic Intergroup (IFCT), Paris, France; 13IHU RespirERA, department of pneumology, Nice Hospital, University Côte d'Azur, Nice, France; 14Institut du Thorax Curie-Montsouris, Institut Curie, Paris, France; 15Cancer Medicine Department, Gustave Roussy, Villejuif, France; 16Department of Pathology, Necker hospital, AP-HP, Université Paris Cité, Paris, France

Correspondence to: Véronique Hofman, MD, PhD. IHU RespirERA, LPCE, avenue voie Romaine, Nice Hospital, University Côte d'Azur, Nice, 6000, France. Email: hofman.v@chu-nice.fr.

Background: Thymic epithelial tumors (TETs) are rare tumors with variable aggressiveness. More than 30% of the patients develop metastases requiring systemic treatment. Previously, a few clinical trials evaluated different FGFR kinase inhibitors showing diverse promising results. FGFR1 amplification is found in around 20% of lung squamous cell carcinomas (LSCC) representing a potential therapeutic target of these tumors. In this context, squamous cell thymic carcinomas (TCs) showing an FGFR1 amplification could be eligible to target therapy. The purpose of this article is to analyse the presence of FGFR1 amplification in TET with clinical, pathological and prognosis factors correlation.

Methods: Forty-eight specimens from surgically resected patients with diagnosis of TET validated by RYTHMIC national tumor board from January 2009 to May 2015 were included. Specimens were centrally reviewed by a panel of expert pathologists with diagnoses made according to the 2021 World Health Organization (WHO) histological classification. FGFR1 amplification was performed by fluorescence in situ hybridization (FISH) (ZytoLight-Clinisciences). The slides were scanned and analysed by two independent observers.

Results: Among 48 specimens (31 squamous TC and 17 B3 thymoma), 6/48 (12.5%) tumors were FGFR1 amplified [5/31 TC (16%) and 1/17 B3 thymoma (6%)]. All these cases demonstrated low-level amplification, with polysomy (≥2 CEN8 signals on average). FGFR1/CEN8 ratios ranged from 1.01 to 1.5 (≤2). No significant differences were observed between the two groups (amplified or not) according to age, gender, autoimmune disease, histology, and stage. The median follow-up was 97 months (range, 73–186 months). Median progression-free survival (PFS) was similar between the two groups (43.2 vs. 42.7 months, amplified vs. non-amplified, respectively) and median overall survival was not significantly different (132 months in the amplification-positive group vs. 79.2 months; P=0.72) these results should be interpreted however with caution due to the small sample size of the series and FGFR1 amplified cases.

Conclusions: In our series, FGFR1 amplification detected by FISH was found in 16% of TC and 6% of thymoma. TETs level amplification is much lower than in LSCC and is associated with a polysomy in all cases. This molecular alteration is potentially targetable similar to the FGFR3 and should be therefore potentially evaluated in refractory TC or thymoma.

Keywords: Thymic epithelial tumors (TETs); FGFR1 amplification; thymic carcinoma (TC); fluorescence in situ hybridization (FISH)

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-25-ab055/coif). V.T.d.M. serves as an unpaid editorial board member of Mediastinum from May 2025 to December 2026. N.G. and T.J.M. serve as unpaid editorial board members of Mediastinum from January 2024 to December 2025. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by a national ethics committee for observational studies (Comité d’Evaluation des Protocoles de Recherche Observationnelle, CEPRO) on 18/12/2014, by the French Advisory Committee on Information Processing in Material Research in the Field of Health (Comité Consultatif sur le Traitement de l'Information en Matière de Recherche dans le Domaine de la Santé, CCTIRS) on 17/03/2016 and by the National Commission of Informatics and Liberty (CNIL) on 24/05/2016, according to French laws. The patients included in this study received information from their referring clinician, as recommended by competent authorities, that specified that, according to French laws, they were allowed to ask for complete access to/removal of their own collected data. Individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

doi: 10.21037/med-25-ab055
Cite this abstract as: Hofman V, Chalabreysse L, Dales JP, Dubois R, Mansuet-Lupo A, de Muret A, Piton N, Rouquette I, Secq V, Sizaret D, Thomas de Montpréville V, Millière A, Lalvé S, Missy P, Lemattre C, Benzaquen J, Hofman P, Girard N, López-Gutiérrez Á, Besse B, Molina TJ. AB055. FGFR1 amplification in thymic epithelial tumors (TETs): a study from 48 cases. Mediastinum 2025;9:AB055.

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