Molecular analyses of biliary tract cancers indicate that neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare, suggesting that it is not a major driver of BTC pathogenesis.
The neurotrophic tyrosine receptor kinase (NTRK) gene fusions have been identified in approximately 1% of solid tumors and have been previously reported in biliary tract cancers (BTCs). These alterations are actionable since NTRK inhibitors, such as larotrectinib (Vitrakvi), have demonstrated antitumor activity in different cancer types. Therefore, the incidence and molecular characteristics of NTRK gene fusions in patients with BTCs were determined and reported at the American Society of Clinical Oncology (ASCO) 2020 Gastrointestinal Cancers Symposium.
In this study, formalin-fixed paraffin-embedded archival blocks of BTC tumors were retrieved from the tumor bank of the CUB Hôpital Erasme, Anderlecht, Belgium, between January 2010 and July 2019. BTC tumors included intrahepatic CCA, extrahepatic CCA, perihilar CCA, and gallbladder tumors. A 2-step diagnostic method was adopted, first incorporating IHC screening using pan-TRK monoclonal antibody and scoring staining intensity (negative, weak, moderate, or strong), followed by NGS analysis with an RNA-based next-generation sequencing panel in samples with at least weak staining tumor cells.
A total of 162 archival tumor samples from different sources were included in the analysis, including 88 samples from surgical resections, 56 samples from biopsies, and 18 from cytology. Of these, 66 samples had a diagnosis of intrahepatic CCA, 36 samples had perihilar CCA, 33 samples had extrahepatic CCA, and 27 samples had gallbladder tumors. Of the 162 selected samples, 149 samples were suitable to perform IHC; of which, 17 samples were IHC-positive, including 9 samples in intrahepatic CCA, 3 samples in perihilar CCA, 2 samples in extrahepatic CCA, and 3 samples in gallbladder tumors. Intensity of staining was weak in 16 samples and moderate in 1.
NGS testing performed in the 17 IHC-positive samples revealed a single NTRK3 gene fusion, ETV6-NTRK3. Overall, the incidence of NTRK fusions in BTCs was 0.67%, using the 2-step diagnostic method of IHC screening and NGS confirmation in this data set.
These results indicate that NTRK gene fusions are rare in BTCs and support the utility of NGS to confirm IHC results.
Source: Demols A, et al. J Clin Oncol. 2020;38(suppl_4). Abstract 574.
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