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Sökning: WFRF:(Karlsson Edlund Patrick) > (2016) > Inconsistent result...

  • Mattsson, Johanna Sofia Margareta,1985-Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (författare)

Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

  • Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

  • 2016-08-05
  • London, United Kingdom :Springer Science and Business Media LLC,2016
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-284591
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-284591URI
  • https://doi.org/10.1186/s12885-016-2646-xDOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-51613URI
  • https://lup.lub.lu.se/record/fca806a9-32f5-40eb-b1d2-07457ccae1a1URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:134010465URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agency:Lions Cancer Foundation, Uppsala, SwedenRegional Research Foundation of the Uppsala Örebro region RFR 556381
  • Background: Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data.Methods: ALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients.Results: ALK rearrangements were detected in 1.7% in the complete cohort and 2.0% in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.9% and 1.5% when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (>99%), while the sensitivity was between 69% (Ventana) and 62% (in house Dako protocol). Furthermore, only 67% of the ALK IHC positive cases were positive in both IHC assays. Gene expression analysis revealed that 6/194 (3%) tumors showed high ALK gene expression (≥6AU) and of them only three were positive by either FISH or IHC.Conclusion: The overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Brunnström, HansLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-hsb (författare)
  • Jabs, VerenaTU Dortmund Univ, Dept Stat, Dortmund, Germany,Department of Statistics, TU Dortmund University, Dortmund, Germany,Technical University of Dortmund (författare)
  • Edlund, KarolinaDortmund TU, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany,Leibniz Research Centre for Working Environment and Human Factors (IfADo) at Dortmund TU, Dortmund, Germany,Technical University of Dortmund (författare)
  • Jirström, KarinLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-kji (författare)
  • Mindus, StephanieUppsala University,Uppsala universitet,Lungmedicin och allergologi,Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden (författare)
  • La Fleur, LinneaUppsala University,Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Johan Botling,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden(Swepub:uu)linla513 (författare)
  • Ponten, FredrikUppsala University,Uppsala universitet,Klinisk och experimentell patologi,Fredrik Pontén,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden(Swepub:lu)tbio-fip (författare)
  • Karlsson, Mats G.,1960-Örebro University,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Research and Education,Univ Orebro, Fac Med & Hlth, Dept Res & Educ, Orebro, Sweden(Swepub:oru)mskn (författare)
  • Karlsson, Christina,1968-Örebro University,Örebro universitet,Institutionen för hälsovetenskaper,Univ Orebro, Sch Hlth Sci, Orebro, Sweden(Swepub:oru)ckn (författare)
  • Koyi, HirshKarolinska Institutet,Uppsala University,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden,Department of Respiratory Medicine, Gävle hospital, Gävle, Sweden; Centre for Research and Development, Uppsala University, Uppsala, Sweden; County Council of Gävleborg, Gävle, Sweden(Swepub:uu)hirko843 (författare)
  • Brandén, EvaUppsala University,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden,Department of Respiratory Medicine, Gävle hospital, Gävle, Sweden; Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle, Sweden(Swepub:uu)evabr789 (författare)
  • Botling, JohanUppsala University,Uppsala universitet,Klinisk och experimentell patologi,Johan Botling,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden(Swepub:uu)johanbot (författare)
  • Helenius, Gisela,1973-Örebro University,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden,Univ Orebro, Fac Med & Hlth, Dept Lab Med, Orebro, Sweden(Swepub:oru)ghs (författare)
  • Micke, PatrickUppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden(Swepub:uu)patmi676 (författare)
  • Svensson, MariaÖrebro University (författare)
  • Uppsala universitetKlinisk och experimentell patologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:BMC CancerLondon, United Kingdom : Springer Science and Business Media LLC161471-2407

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