71P NTRK gene fusions in bilio-pancreatic cancers

Gene fusions involving one of the 3 neurotrophic tyrosine receptor kinases (NTRK) have been identified in ≈1% of solid tumors and inhibitors of TRK have been shown to have anti-tumor activity regardless of tumor type. NTRK gene fusions have been previously reported in bilio-pancreatic cancers. It is of interest therefore to determine incidence and molecular characteristics of NTRK gene fusions in these tumors. Formalin-fixed paraffin-embedded archival blocks from surgical resections or biopsies samples of biliary tract tumors (BTC), and pancreatic adenocarcinoma (PA) were retrieved from the tumor bank of the CUB Hôpital Erasme between JAN 2010 and OCT 2019. A two-step diagnostic method incorporating immunohistochemistry (IHC) screening followed by NGS analysis was used. Pan–TRK IHC (mAb clone EPR17341 [AbCam, Cambridge, MA]) was used for the screening method. Staining intensity, pattern and localization were evaluated. Presence of at least weak staining tumor cells led to testing by a RNA-based NGS panel (Oncomine Focus Assay, Thermo Fisher scientific). For BTC, 162 tumors samples have been selected, 149 were suitable to perform IHC. 17 samples were IHC positive. Intensity of staining was weak in 16 cases and moderate in one. Staining location was cytoplasmic (14/17), nuclear (2/17), and nuclear+cytoplasmic (1/17). Pattern of staining was rare positive cells (2/17), focal (4/17) and diffuse (11/17). NGS testing of the 17 IHC positive cases revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)). In this peri-hilar tumor, IHC had a weak focal cytoplasmic and nuclear staining. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.67 %. For PA, 319 tumor samples have been selected, 297 were suitable to perform IHC. 19 samples were IHC positive. Intensity of staining was weak in 18 cases and moderate in one. Staining location was cytoplasmic (18/19) and nuclear (1/19). Pattern of staining was focal in 2 and diffuse in 17 cases. No fusion was detected by NGS. NTRK gene fusions are rare in bilio-pancreatic cancers. But testing is of high interest due to the emergence of possible treatment with specific TRK inhibitors. These results support the use of NGS to confirm positive IHC results during diagnostic screening.