Journal
EUROPEAN JOURNAL OF CANCER
Volume 166, Issue -, Pages 165-175Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2022.02.013
Keywords
Biliary tract cancers; FGFR2; Biomarkers; NGS
Categories
Funding
- QED Therapeutics (San Francisco, CA)
- Veneto Region [NET-2016e02363853]
- Italian Association for Cancer Research AIRC [22759]
- Italian Health Ministry
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A study of 286 patients with biliary tract cancer revealed that FGFR2/3 aberrations and IDH1/2 mutations may serve as prognostic factors for survival in these patients. The recognition and assessment of their prognostic impact is important for the interpretation of existing data and the design of new therapeutic trials.
Aim: FGFR2 rearrangements have been identified as a novel therapeutic target of biliary tract cancer (BTC). However, reliable prevalence estimates of this molecular alteration and its prognostic role have not been fully elucidated. Methods: A retrospective mono-institutional series of 286 patients affected by locally advanced or metastatic BTC (183 intrahepatic cholangiocarcinomas, 67 extrahepatic cholangiocarcinomas, 36 gallbladder carcinomas) was profiled by means of targeted DNA/RNA next-generation sequencing, immunohistochemistry and fluorescence in situ hybridisation for FGFR2/3, ERBB2, NTRK alterations, IDH1/2 and BRAF mutations and DNA mismatch repair complex proteins alterations/microsatellite instability. Results: FGFR2 rearrangements, amplifications and point mutations were detected in 15 (5.2 %), 1 and 3 cases, respectively. FGFR3 alterations were observed in 5 (1.7%) cases. IDH1/2 were mutated in 35/223 cases (15.7%). A total of 9/258 (3.5%) and 6/260 (2.3%) BTCs had ERBB2 and BRAF gene alterations, respectively. Two cases (2/242; 0.8%) had NTRK1 amplifications but no rearrangement was found. A deficit of mismatch repair protein expres-sion was identified in 9/237 cases (3.8%). At multivariate analysis, age, ECOG performance status, number of metastatic sites, tumour stage, FGFR2/3 alterations and IDH1/2 mutations were prognostic factors of overall survival. Conclusions: These data provide a strong proof -challenged with a robust and detailed multi-variate model -that FGFR2/3 aberrations (including FGFR2 rearrangements) and IDH1/2 mutations can be prognostic for better survival in patients with BTC . The recognition and the measurement of their prognostic impact could be of primary importance for the correct interpretation of currently available data and in the design of new therapeutic trials.@ 2022 Elsevier Ltd. All rights reserved.
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