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ePoster Display

444P - Prevalence of NTRK1/2/3 fusions in dMMR/MSI metastatic colorectal cancer


16 Sep 2021


ePoster Display


Magali Svrcek


Annals of Oncology (2021) 32 (suppl_5): S530-S582. 10.1016/annonc/annonc698


M. Svrcek1, R. Colle2, A. Cayre3, L. Mas2, P. Bourgoin1, R. Cohen4, T. André5, F. Penault-Llorca6, N. Radosevic-Robin3

Author affiliations

  • 1 Pathology, Sorbonne Université, Hopital Saint-Antoine, 75012 - Paris/FR
  • 2 Oncology, Sorbonne Université, hôpital Saint-Antoine, 75012 - Paris/FR
  • 3 Pathology, University Clermont Auvergne, INSERM U1240, Centre Jean Perrin,, 63011 - Clermont-Ferrand/FR
  • 4 Medical Oncology Department, Hôpital Saint-Antoine, 75571 - Paris/FR
  • 5 Medical Oncology Department, Hopital Saint-Antoine, 75571 - Paris/FR
  • 6 Direction Generale/bp 392, Jean Perrin Center, 63011 - Clermont-Ferrand/FR

Abstract 444P


Inhibitors of tropomyosin receptor kinase (TRK) have shown promising activity against neurotrophic TRK (NTRK) fusion-driven cancers. NTRK gene fusions are observed in less than 1% of colorectal cancers (CRCs). CRCs harboring wild-type BRAF, KRAS and MisMatch Repair deficiency (dMMR)/MicroSatellite Instability (MSI) due to MLH1 hypermethylation have been associated with NTRK fusions in small cohorts of non-metastatic tumors. We evaluated the frequency and associated clinical characteristics of NTRK fusions among dMMR/MSI metastatic CRCs (mCRCs) patients (pts).


Tumor samples of dMMR/MSI mCRC pts were obtained from a French multicenter retrospective cohort and from a single-center cohort of pts treated with immune checkpoint inhibitors (ICIs). Clinico-pathological data including KRAS and BRAF V600E status, MMR protein and MLH1 methylation status were available for all pts. All samples were screened for TRK expression by immunohistochemistry (IHC) using a pan-TRK antibody (clone EPR17341, Abcam) and for NTRK1/2/3 gene rearrangements, by FISH. Targeted RNAseq (FusionPlex® Lung SK0133 ARCHER kit) was performed on IHC or FISH-positive and doubtful cases.


A total of 172 pts [paired samples (primary + metastasis): n=38; primary only: n=134] were screened. Tumor samples of 10 pts (5.8%) harbored NTRK fusion genes by FISH (NTRK1=8; NTRK3=2), out of which only 5 were pan-TRK+. Archer assay detected TPM3-NTRK1 (n=2), LMNA-NTRK1 (n=2), ETV6-NTRK3 (n=1) and EML4-NTRK3 (n=1) fusion transcripts in 6 pts, including 4 cases pan-TRK+. Eight cases were sporadic and two had germline MMR mutations (Lynch syndrome) with loss of MSH2/MSH6 and isolated loss of MSH6 expression, respectively. One Lynch-related tumor was KRAS mutated, one sporadic tumor was BRAF V600E mutated. Four NTRK positive pts received ICIs, resulting in 3 objective responses per iRECIST (two complete and one partial responses with 25 to 54 months of follow up) and one primary resistance.


Frequency of NTRK1/2/3 fusions was 5.8% in our dMMR/MSI mCRCs cohort. These fusions were not restricted to sporadic cases. The diagnostic accuracy of pan-TRK IHC was low. Optimal testing algorithms for theranostic purpose remain to be defined in this setting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Magali Svrcek.




R. Cohen: Financial Interests, Personal, Advisory Board: Amgen; Sanofi. T. André: Financial Interests, Personal, Invited Speaker: BMS; HalioDx; Roche; Sanofi. F. Penault-Llorca: Financial Interests, Personal, Research Grant, consulting and travels: Bayer; Financial Interests, Personal, Advisory Board, Research funding and travels: Nanostring; Financial Interests, Personal, Research Grant, Advisory board: Illumina; Financial Interests, Personal, Advisory Role, Travels: Roche. All other authors have declared no conflicts of interest.

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