Evidence map›Paper›PMID 31792356›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2020

NTRK gene rearrangements are highly enriched in MLH1/PMS2 deficient, BRAF wild-type colorectal carcinomas-a study of 4569 cases.

Angela Chou, Tamara Fraser, Mahsa Ahadi, Talia Fuchs, Loretta Sioson, Adele Clarkson, Amy Sheen, Nisha Singh, Christopher L Corless, Anthony J Gill

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 69 citations in OpenAlex.

  1. Trial
  2. Annals of medicine and surgery (2012) · 2026
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  17. Detection ofDiagnostics (Basel, Switzerland) · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Angela ChouCancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
Tamara FraserCancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
Mahsa AhadiCancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.ORCID http://orcid.org/0000-0002-4687-8666
Talia FuchsCancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.ORCID http://orcid.org/0000-0002-9166-6822
Loretta SiosonCancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
Adele ClarksonCancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
Amy SheenCancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
Nisha SinghNSW Health Pathology, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
Christopher L CorlessDepartment of Pathology and Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA.
Anthony J GillCancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia. affgill@med.usyd.edu.au.ORCID http://orcid.org/0000-0002-9447-1967
Royal North Shore Hospital · AUThe University of Sydney · AUOregon Health & Science University · USUniversity of Technology Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

NTRK gene rearrangements are important to identify as predictors of response to targeted therapy in many malignancies. Only 0.16-0.3% of colorectal carcinomas (CRCs) harbor these fusions making universal screening difficult. We therefore investigated whether pan-Trk immunohistochemistry (IHC), mismatch repair deficiency (MMRd), and BRAFV600E mutation status could be used to triage molecular testing for NTRK gene rearrangements in CRC. CRCs from 4569 unselected patients underwent IHC in TMA format with two different anti-pan-Trk rabbit monoclonal antibodies. All positive cases were confirmed on whole sections and underwent RNA-sequencing. Pan-Trk IHC was positive in 0.2% of CRCs (9/4569). Both antibodies demonstrated similar staining characteristics with diffuse positive staining in all neoplastic cells. Of note 8/9 (89%) IHC positive cases were both MMRd (all showing MLH1/PMS2 loss) and lacked BRAFV600E mutation. That is, IHC was positive in 5.3% (8/152) MLH1/PMS2/BRAFV600E triple negative CRCs, but only 0.02% (1/4417) not showing this phenotype. All nine IHC positive CRCs demonstrated gene rearrangements (LMNA-NTRK1 in 5 CRCs, TPR-NTRK1, STRM-NTRK1, MUC2-NTRK2, and NTRK1 with an unknown partner in one each), suggesting close to 100% specificity for IHC in this sub-population. NTRK fusions were associated with right sided (p = 0.02), larger tumors (p = 0.029) with infiltrative growth (p = 0.021). As a part of universal Lynch syndrome screening many institutions routinely test all CRCs for MMRd, and then proceed to reflex BRAFV600E mutation testing in MLH1/PMS2 negative CRCs. We conclude that performing pan-Trk IHC on this preselected subgroup of MLH1/PMS2/BRAFV600E triple negative CRCs (only 3.3% of all CRC patients) is a resource effective approach to identify the overwhelming majority of CRC patients with NTRK gene fusions.

Indexed as

AdultAgedBiomarkers, TumorColorectal NeoplasmsFemaleGene RearrangementHumansMaleMiddle AgedMismatch Repair Endonuclease PMS2MutL Protein Homolog 1Oncogene Proteins, FusionProto-Oncogene Proteins B-rafReceptor, trkABiomarkers, TumorBRAF protein, humanMismatch Repair Endonuclease PMS2MLH1 protein, humanMutL Protein Homolog 1Oncogene Proteins, FusionPMS2 protein, humanProto-Oncogene Proteins B-rafReceptor, trkA

Identifiers

PMID31792356
OpenAlexW2990680197

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.