A Two-Step Diagnostic Approach for NTRK Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas

Sep 24, 2026

Uploaded by Connor

The study evaluates the incidence and molecular profile of NTRK gene fusions in bilio-pancreatic cancers due to potential responsiveness to TRK inhibitors in advanced disease. An NTRK testing algorithm was implemented using immunohistochemistry screening on archival biliary tract and pancreatic adenocarcinoma samples, followed by RNA-based NGS panels for IHC-positive cases. Across 437 screened cases, NTRK fusions were rare (overall 0.7%), with one confirmed NTRK3 fusion in perihilar cholangiocarcinoma and none in pancreatic cancers.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages6

Reading Time15 min

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Abstract

Background

Methods

Results

Conclusion

Implications for Practice

Introduction

A Two-Step Diagnostic Approach for NTRK Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas Anne Demols1, Laureen Rocq2, Luis Perez-Casanova2, Manon Charry2, Nancy De Nève2, Ali Ramadhan2, Claude Van Campenhout2, Sarah De Clercq2, Calliope Maris2, Jean Closset3, Valerio Lucidi4, Isabelle Salmon2, Nicky D’Haene*,2, 1Department of Gastroenterology and GI Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium 2 Pathology Department, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium 3Digestive Surgery Department, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium 4Digestive Surgery, Hepatobiliary Surgery & Liver Transplantation Department, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium *Corresponding author: Nicky D’Haene, MD, PhD, Laboratory of Pathology, Erasme University Hospital, 808 Route de Lennik, 1070 Brussels, Belgium. Tel: +00 32 2 555 31 15; Fax: 00 32 2 555 47 90; Email: [nicky.d.haene@erasme.ulb.ac.be](nicky.d.haene@erasme.ulb.ac.be) Abstract Background: It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. Methods: Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. Results: For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion ( ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangiocarcinoma, IHC performed on a biopsy showed a weak focal cytoplasmic and nuclear staining. No other NTRK fusion was detected on the 16 other samples with both panels. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.7% . For pancreatic cancers, 319 samples have been selected and 297 were suitable to perform IHC. Nineteen samples were IHC positive. No fusion was detected by NGS. Conclusion: NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to possible treatment with specific TRK inhibitors. Key words: NTRK; NTRK gene fusions; immunohistochemistry; NGS; RNA-based NGS panels; biliary tract and pancreatic adenocarcinomas. Implications for Practice The present study used the diagnostic approach proposed by different guidelines, that is, screening by immunohistochemistry and targeted RNA next-generation sequencing for immunohistochemical positive cases, to study the incidence of NTRK gene fusions in biliopancreatic cancers. This approach allowed the detection of one case with an NTRK gene fusion on a series of 437 bilio-pancreatic cancers, including cytologies, biopsies, and resections. Even if NTRK gene fusions are rare in bilio-pancreatic cancers, it is of high interest to detect them because of possible treatment for advanced tumors with specific TRK inhibitors that are FDA and EMA approved. Introduction The tropomyosin receptor kinase (TRK) receptor family comprises 3 transmembrane proteins referred to as TRK A, B, and C (TRKA, TRKB, and TRKC) receptors that are encoded by the NTRK 1, NTRK2, and NTRK3 genes, respectively.1,2 These tyrosine kinase receptors are expressed in human neuronal tissue and play an essential role in the physiology of development and function of the nervous system.2 After embryogenesis, the expression of TRK proteins is limited to the nervous system, testis,

FAQs

What was the goal of this study on NTRK gene fusions in bilio-pancreatic cancers?

To apply an NTRK testing algorithm and determine the incidence and molecular characteristics of NTRK gene fusions, motivated by possible treatment with TRK inhibitors for advanced tumors.

How were patients screened and confirmed for NTRK gene fusions?

Samples were first screened by immunohistochemistry (IHC); cases with at least weak staining in rare tumor cells were then tested using two RNA-based NGS panels.

What were the key findings for biliary tract tumors and pancreatic cancers?

Among biliary tract tumors, 17 were IHC positive and one NTRK3 fusion (ETV6(4)-NTRK3(14)) was detected by both NGS panels; the overall fusion rate was 0.7%. For pancreatic cancers, 19 were IHC positive, but no NTRK fusion was detected by NGS.

Sep 24, 2026

Uploaded by Connor