Molecular detection and clinicopathological characteristics of advanced/recurrent biliary tract carcinomas harboring the FGFR2 rearrangements: a prospective observational study (PRELUDE Study)

Autor: Maruki, Yuta, Morizane, Chigusa, Arai, Yasuhito, Ikeda, Masafumi, Ueno, Makoto, Ioka, Tatsuya, Naganuma, Atsushi, Furukawa, Masayuki, Mizuno, Nobumasa, Uwagawa, Tadashi, Takahara, Naminatsu, Kanai, Masashi, Asagi, Akinori, Shimizu, Satoshi, Miyamoto, Atsushi, Yukisawa, Seigo, Kadokura, Makoto, Kojima, Yasushi, Furuse, Junji, Nakajima, Takako Eguchi, Sudo, Kentaro, Kobayashi, Noritoshi, Hama, Natsuko, Yamanaka, Takeharu, Shibata, Tatsuhiro, Okusaka, Takuji
Rok vydání: 2020
Předmět:
Zdroj: Journal of Gastroenterology
ISSN: 1435-5922
0944-1174
Popis: Background Fibroblast growth factor receptor 2 (FGFR2) rearrangement is expected to be a novel therapeutic target in advanced/recurrent biliary tract cancer (BTC). However, efficient detection and the exact frequency of FGFR2 rearrangements among patients with advanced/recurrent BTC have not been determined, and the clinical characteristics of FGFR2 rearrangement-positive patients have not been fully elucidated. We aimed to determine the frequency of FGFR2 rearrangement-positive patients among those with advanced/recurrent BTC and elucidate their clinicopathological characteristics. Methods Paraffin-embedded tumor samples from formalin-fixed surgical or biopsy specimens of patients with advanced/recurrent BTC were analyzed for positivity of FGFR2 rearrangement by fluorescent in situ hybridization (FISH). RNA sequencing was performed on samples from all FISH-positive and part of FISH-negative patients. Results A total of 445 patients were enrolled. FISH was performed on 423 patients (272 patients with intrahepatic cholangiocarcinoma (ICC), 83 patients with perihilar cholangiocarcinoma (PCC), and 68 patients with other BTC). Twenty-one patients with ICC and four patients with PCC were diagnosed as FGFR2-FISH positive. Twenty-three of the 25 FISH-positive patients (20 ICC and 3 PCC) were recognized as FGFR2 rearrangement positive by targeted RNA sequencing. Younger age (≤ 65 years; p = 0.018) and HCV Ab- and/or HBs Ag-positivity (p = 0.037) were significantly associated with the presence of FGFR2 rearrangement (logistic regression). Conclusions FGFR2 rearrangement was identified in ICC and PCC patients, and was associated with younger age and history of hepatitis viral infection.
Databáze: OpenAIRE
Externí odkaz: