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Evaluation of NTRK ...
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Elfving, HedvigUppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Patrick Micke
(author)
Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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Elsevier,2021
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-431535
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-431535URI
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https://doi.org/10.1016/j.lungcan.2020.11.023DOI
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https://lup.lub.lu.se/record/f1878477-5df8-4318-9ea2-9691604e6239URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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De två första författarna delar förstaförfattarskapet
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Purpose: The small molecule inhibitors larotrectinib and entrectinib have recently been approved as cancer agnostic drugs in patients with tumours harbouring a rearrangement of the neurotrophic tropomyosin receptor kinase (NTRK). These oncogenic fusions are estimated to occur in 0.1-3 % of non-small cell lung cancers (NSCLC). Although molecular techniques are most reliable for fusion detection, immunohistochemical analysis is considered valuable for screening. Therefore, we evaluated the newly introduced diagnostic immunohistochemical assay (clone EPR17341) on a representative NSCLC cohort.Methods: Cancer tissue from 688 clinically and molecularly extensively annotated NSCLC patients were comprised on tissue microarrays and stained with the pan-TRK antibody clone EPR17341. Positive cases were further analysed with the TruSight Tumor 170 RNA assay (Illumina). Selected cases were also tested with a NanoString NTRK fusion assay. For 199 cases, NTRK RNA expression data were available from previous RNA sequencing analysis.Results: Altogether, staining patterns for 617 NSCLC cases were evaluable. Of these, four cases (0.6 %) demonstrated a strong diffuse cytoplasmic and membranous staining, and seven cases a moderate staining (1.1 %). NanoString or TST170-analysis could not confirm an NTRK fusion in any of the IHC positive cases, or any of the cases with high mRNA levels. In the four cases with strong staining intensity in the tissue microarray, whole section staining revealed marked heterogeneity of NTRK protein expression.Conclusion: The presence of NTRK fusion genes in non-small cell lung cancer is exceedingly rare. The use of the immunohistochemical NTRK assay will result in a small number of false positive cases. This should be considered when the assay is applied as a screening tool in clinical diagnostics.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Broström, ErikaUppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)eribr175
(author)
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Moens, Lotte N.J.Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Johan Botling(Swepub:uu)lotmo617
(author)
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Almlöf, JonasUppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi(Swepub:uu)jonca820
(author)
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Cerjan, DijanaUppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)dijce981
(author)
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Lauter, GilbertUppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Johan Botling(Swepub:uu)gilla825
(author)
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Nord, Helena,1980-Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Johan Botling(Swepub:uu)helno987
(author)
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Mattsson, Johanna S. M.,1985-Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Patrick Micke(Swepub:uu)johma961
(author)
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Ullenhag, Gustav J.Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala University Hospital(Swepub:uu)gustulle
(author)
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Strell, CarinaUppsala University(Swepub:uu)carst810
(author)
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Backman, MaxUppsala University,Patrick Micke(Swepub:uu)maxba655
(author)
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La Fleur, LinnéaUppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Johan Botling(Swepub:uu)linla513
(author)
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Brunnström, HansLund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)med-hsb
(author)
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Botling, JohanUppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Johan Botling(Swepub:uu)johanbot
(author)
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Micke, PatrickUppsala University,Patrick Micke(Swepub:uu)patmi676
(author)
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Uppsala universitetInstitutionen för immunologi, genetik och patologi
(creator_code:org_t)
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In:Lung Cancer: Elsevier151, s. 53-590169-50021872-8332
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Elfving, Hedvig
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Broström, Erika
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Moens, Lotte N.J ...
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Almlöf, Jonas
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Cerjan, Dijana
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Lauter, Gilbert
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Nord, Helena, 19 ...
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Strell, Carina
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Backman, Max
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La Fleur, Linnéa
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Brunnström, Hans
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Micke, Patrick
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