Mazzoni Francesca, Petreni Paolo, Vasile Enrico, Panebianco Michele, Casadei-Gardini Andrea, Negri Francesca, Lunghi Alice, Pillozzi Serena, Vivaldi Caterina, Gervasi Erika, Frassineti Giovanni Luca, Messerini Luca, Jocollé Genny, Bisagni Alessandra, Antonuzzo Lorenzo, Rossi Giulio
Medical Oncology Unit, AOU Careggi Hospital, I-50134 Florence, Italy.
Medical Oncology Unit, Alta Val d'Elsa Hospital, I-53036 Poggibonsi, Italy.
Oncol Lett. 2020 Dec;20(6):316. doi: 10.3892/ol.2020.12179. Epub 2020 Oct 1.
Biliary tract cancers (BTCs) are a pool of diseases with poor prognosis and there is no orphan drug available. Currently, no molecular targets have been tested as druggable oncogenic drivers. C-ros oncogene 1 () rearrangements have been previously described in various tumors, including BTCs; however, data regarding their incidence and biological significance are controversial. Therefore, a retrospective multicenter study was performed to assess the incidence of rearrangements in BTCs by means of immunohistochemistry and fluorescence hybridization (FISH). The present study failed to demonstrate ROS1 expression in a multicenter series of 150 cases with BTCs and revealed that D4D6 was the most specific clone compared with other ROS1 primary antibodies, namely PA1-30318 and EPMGHR2. Notably, negative results obtained with D4D6 completely matched to data sorted out by FISH analysis, thus confirming a lack of gene rearrangements in BTCs and false positive results when PA1-30318 and EPMGHR2 clones were used. These results suggest that rearrangements may not be targets for molecular therapy of BTCs with specific inhibitors.
胆管癌（BTCs）是一类预后较差的疾病，且尚无孤儿药可用。目前，尚无分子靶点被作为可成药的致癌驱动因子进行测试。C-ros癌基因1（ROS1）重排在包括胆管癌在内的多种肿瘤中均有过报道；然而，关于其发生率及生物学意义的数据存在争议。因此，开展了一项回顾性多中心研究，旨在通过免疫组织化学和荧光原位杂交（FISH）评估胆管癌中ROS1重排的发生率。本研究未能在150例胆管癌多中心病例系列中证实ROS1表达，并显示与其他ROS1一抗（即PA1-30318和EPMGHR2）相比，D4D6是最具特异性的克隆。值得注意的是，D4D6得到的阴性结果与FISH分析整理的数据完全匹配，从而证实胆管癌中不存在ROS1基因重排，以及使用PA1-30318和EPMGHR2克隆时出现的假阳性结果。这些结果表明，ROS1重排可能不是胆管癌特异性抑制剂分子治疗的靶点。
