Molecular detection and clinicopathological characteristics of advanced/recurrent biliary tract carcinomas harboring the FGFR2 rearrangements: a prospective observational study (PRELUDE Study).
Molecular detection and clinicopathological characteristics of advanced/recurrent biliary tract carcinomas harboring the FGFR2 rearrangements: a prospective observational study (PRELUDE Study).
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DOI：
10.1007/s00535-020-01735-2
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发表时间：
2021-03
影响因子：
6.3
通讯作者：
Okusaka T
中科院分区：
文献类型：
--
作者：
Maruki Y;Morizane C;Arai Y;Ikeda M;Ueno M;Ioka T;Naganuma A;Furukawa M;Mizuno N;Uwagawa T;Takahara N;Kanai M;Asagi A;Shimizu S;Miyamoto A;Yukisawa S;Kadokura M;Kojima Y;Furuse J;Nakajima TE;Sudo K;Kobayashi N;Hama N;Yamanaka T;Shibata T;Okusaka T
成纤维细胞生长因子受体2（FGFR 2）重排有望成为晚期/复发性胆道癌（BTC）治疗的新靶点。然而，尚未确定晚期/复发性BTC患者中FGFR 2重排的有效检测和确切频率，FGFR 2重排阳性患者的临床特征尚未完全阐明。我们的目的是确定FGFR 2再表达阳性患者在晚期/复发性BTC患者中的频率，并阐明其临床病理学特征。通过荧光原位杂交（FISH）分析来自福尔马林固定的晚期/复发性BTC患者的手术或活检标本的石蜡包埋肿瘤样本的FGFR 2重排阳性。对来自所有FISH阳性和部分FISH阴性患者的样品进行RNA测序。共入组445例患者。对423例患者（272例肝内胆管癌（ICC），83例肝门周胆管癌（PCC），68例其他BTC）进行了FISH。21例ICC和4例PCC患者被诊断为FGFR 2-FISH阳性。25例FISH阳性患者中有23例（ICC 20例，PCC 3例）经靶向RNA测序确认为FGFR 2重排阳性。年轻（≤ 65岁; p = 0.018）和HCV Ab和/或HBs Ag阳性（p = 0.037）与FGFR 2重排的存在显著相关（logistic回归）。在ICC和PCC患者中发现了FGFR 2重排，并且与年龄较小和肝炎病毒感染史相关。本文的在线版本（10.1007/s 00535 -020-01735-2）包含补充材料，可供授权用户使用。
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. 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. 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). FGFR2 rearrangement was identified in ICC and PCC patients, and was associated with younger age and history of hepatitis viral infection. The online version of this article (10.1007/s00535-020-01735-2) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/s1470-2045(20)30157-1
发表时间：
2020-06
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Abou-Alfa GK;Macarulla T;Javle MM;Kelley RK;Lubner SJ;Adeva J;Cleary JM;Catenacci DV;Borad MJ;Bridgewater J;Harris WP;Murphy AG;Oh DY;Whisenant J;Lowery MA;Goyal L;Shroff RT;El-Khoueiry AB;Fan B;Wu B;Chamberlain CX;Jiang L;Gliser C;Pandya SS;Valle JW;Zhu AX
通讯作者：
Zhu AX
影响因子：
4
作者：
Weiss GJ;Hoff BR;Whitehead RP;Sangal A;Gingrich SA;Penny RJ;Mallery DW;Morris SM;Thompson EJ;Loesch DM;Khemka V
通讯作者：
Khemka V
影响因子：
11.5
作者：
Brooks, A. Nigel;Kilgour, Elaine;Smith, Paul D.
通讯作者：
Smith, Paul D.
DOI：
10.1016/s1470-2045(20)30109-1
发表时间：
2020-05
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Abou-Alfa GK;Sahai V;Hollebecque A;Vaccaro G;Melisi D;Al-Rajabi R;Paulson AS;Borad MJ;Gallinson D;Murphy AG;Oh DY;Dotan E;Catenacci DV;Van Cutsem E;Ji T;Lihou CF;Zhen H;Féliz L;Vogel A
通讯作者：
Vogel A
影响因子：
4.6
作者：
Jain, Apurva;Borad, Mitesh J.;Javle, Milind
通讯作者：
Javle, Milind