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 (ROS1) rearrangements have been previously described in various tumors, including BTCs; however, data regarding their incidence and biological significance are controversial. Therefore, a retrospective multi‑ center study was performed to assess the incidence of ROS1 rearrangements in BTCs by means of immunohistochemistry and fluorescence in situ 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, nega‑ tive results obtained with D4D6 completely matched to data sorted out by FISH analysis, thus confirming a lack of ROS1 gene rearrangements in BTCs and false positive results when PA1‑30318 and EPMGHR2 clones were used. These results suggest that ROS1 rearrangements may not be targets for molecular therapy of BTCs with specific inhibitors.

ROS1 rearrangements are uncommon in biliary tract cancers / Mazzoni, F.; Petreni, P.; Vasile, E.; Panebianco, M.; Casadei Gardini, A.; Negri, F.; Lunghi, A.; Pillozzi, S.; Vivaldi, C.; Gervasi, E.; Frassineti, G. L.; Messerini, L.; Jocolle, G.; Bisagni, A.; Antonuzzo, L.; Rossi, G.. - In: ONCOLOGY LETTERS. - ISSN 1792-1074. - 20:6(2020), pp. 1-10. [10.3892/OL.2020.12179]

ROS1 rearrangements are uncommon in biliary tract cancers

Casadei Gardini A.;Rossi G.
2020-01-01

Abstract

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 (ROS1) rearrangements have been previously described in various tumors, including BTCs; however, data regarding their incidence and biological significance are controversial. Therefore, a retrospective multi‑ center study was performed to assess the incidence of ROS1 rearrangements in BTCs by means of immunohistochemistry and fluorescence in situ 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, nega‑ tive results obtained with D4D6 completely matched to data sorted out by FISH analysis, thus confirming a lack of ROS1 gene rearrangements in BTCs and false positive results when PA1‑30318 and EPMGHR2 clones were used. These results suggest that ROS1 rearrangements may not be targets for molecular therapy of BTCs with specific inhibitors.
2020
Biliary tract cancers
Biomarker
Fluorescence in situ hybridization
Immuno‑ histochemistry
Molecular target
ROS1 rearrangements
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/107555
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