ROS1 gene rearrangements in non-small cell lung cancer immunohistochemistry and fluorescence in situ hybridization

Keuhkosyöpä on maailman yleisin syöpäkuolemien aiheuttaja. Histologisesti se jaetaan pienisoluiseen (15 %) ja ei-pienisoluiseen (85 %) keuhkosyöpään (engl. non-small cell lung cancer, NSCLC). ROS1-geenin uudelleenjärjestäytymät ovat harvinaisia NSCLC:ssä (1–2 %), mutta tärkeitä tunnistaa kohdennettu...

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Päätekijä: Tynkkynen, Niko
Muut tekijät: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Aineistotyyppi: Pro gradu
Kieli:eng
Julkaistu: 2020
Aiheet:
Linkit: https://jyx.jyu.fi/handle/123456789/75830
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author Tynkkynen, Niko
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Tynkkynen, Niko Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Tynkkynen, Niko Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Tynkkynen, Niko
datasource_str_mv jyx
description Keuhkosyöpä on maailman yleisin syöpäkuolemien aiheuttaja. Histologisesti se jaetaan pienisoluiseen (15 %) ja ei-pienisoluiseen (85 %) keuhkosyöpään (engl. non-small cell lung cancer, NSCLC). ROS1-geenin uudelleenjärjestäytymät ovat harvinaisia NSCLC:ssä (1–2 %), mutta tärkeitä tunnistaa kohdennettua hoitoa varten. Immunohistokemia (IHK) ja fluoresenssi in situ hybridisaatio (FISH) ovat yleisiä menetelmiä tutkittaessa ROS1-uudelleenjärjestäytymiä. Potilaat, joilla ei ole ROS1-uudelleenjärjestäytymiä, voidaan sulkea pois IHK-seulonnalla. FISH:ta tarvitaan positiivisten IHK-tulosten varmistuksessa. Tavoitteena oli selvittää ROS1-uudelleenjärjestäytymien esiintyvyys suomalaisessa NSCLC-aineistossa ja verrata IHK:aa ja FISH:ta ROS1-analytiikassa. Monikudosblokit koostuivat 578 leikattujen potilaiden kasvainnäytteistä (319 adenokarsinoomaa, 235 levyepiteelikarsinoomaa, 24 tarkemmin määrittelemätöntä NSCLC:ää), jotka saatiin kahdesta suomalaisesta biopankista. Formaliinilla fiksoidut ja parafiiniin valetut leikkeet värjättiin ROS1-vasta-aineella. IHK:n tulos oli negatiivinen 548 (94,81 %), positiivinen kahdessa näytteessä (0,35 %) ja epäselvä 28 (4,84 %) näytteessä. Positiiviset IHK-tulokset olivat positiivisia FISH:ssa tai toisen sukupolven sekvensoinnissa ja epäselvät IHK-tulokset olivat negatiivisia FISH:ssa. ROS1-uudelleenjärjestäytymien esiintyvyys oli odotettua pienempi (0,35 %, adenokarsinoomissa 0,63). ROS1-IHK:n herkkyys (100 %) ja tarkkuus (96 %) vastasivat hyvin aiempia tuloksia. Vain muutamat IHK-näytteet näyttävät tarvitsevan FISH-varmistuksen. Lung cancer is the leading cause of cancer death worldwide. Histologically, it is divided into small cell (15 %) and non-small cell (85 %) lung cancer (NSCLC). Rearrangements of ROS1 gene are rare (1–2 % of NSCLC), but essential to recognize for targeted therapy. Two common methods to examine ROS1 rearrangements are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The patients without ROS1 rearrangements can be ruled out by IHC screening. FISH is needed to confirm positive IHC results. This study aimed to examine the prevalence of ROS1 rearrangements among a Finnish NSCLC material and to compare IHC and FISH in ROS1 analysis. Tissue microarrays of 578 samples (319 adenocarcinomas, 235 squamous cell carcinomas and 24 NSCLC-not otherwise specified) were obtained from two Finnish biobanks. Only surgically operated patients were included in the material. Formalin fixed and paraffin embedded sections were stained using a ROS1 antibody. IHC was negative in 548 (94.81 %), positive in 2 (0.35 %) and equivocal in 28 (4.84 %) samples. The IHC positive samples were positive in FISH or NGS and equivocal samples were negative in FISH. The prevalence of ROS1 rearrangements was 0.35 % (0.63 % among adenocarcinomas) being less than expected. The sensitivity and specificity of ROS1 IHC were 100 % and 96 % corresponding well with previous results. Only few IHC samples seems to need FISH confirmation.
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Histologisesti se jaetaan pienisoluiseen (15 %) ja ei-pienisoluiseen (85 %) keuhkosy\u00f6p\u00e4\u00e4n (engl. non-small cell lung cancer, NSCLC). ROS1-geenin uudelleenj\u00e4rjest\u00e4ytym\u00e4t ovat harvinaisia NSCLC:ss\u00e4 (1\u20132 %), mutta t\u00e4rkeit\u00e4 tunnistaa kohdennettua hoitoa varten. Immunohistokemia (IHK) ja fluoresenssi in situ hybridisaatio (FISH) ovat yleisi\u00e4 menetelmi\u00e4 tutkittaessa ROS1-uudelleenj\u00e4rjest\u00e4ytymi\u00e4. Potilaat, joilla ei ole ROS1-uudelleenj\u00e4rjest\u00e4ytymi\u00e4, voidaan sulkea pois IHK-seulonnalla. FISH:ta tarvitaan positiivisten IHK-tulosten varmistuksessa. Tavoitteena oli selvitt\u00e4\u00e4 ROS1-uudelleenj\u00e4rjest\u00e4ytymien esiintyvyys suomalaisessa NSCLC-aineistossa ja verrata IHK:aa ja FISH:ta ROS1-analytiikassa. Monikudosblokit koostuivat 578 leikattujen potilaiden kasvainn\u00e4ytteist\u00e4 (319 adenokarsinoomaa, 235 levyepiteelikarsinoomaa, 24 tarkemmin m\u00e4\u00e4rittelem\u00e4t\u00f6nt\u00e4 NSCLC:\u00e4\u00e4), jotka saatiin kahdesta suomalaisesta biopankista. Formaliinilla fiksoidut ja parafiiniin valetut leikkeet v\u00e4rj\u00e4ttiin ROS1-vasta-aineella. IHK:n tulos oli negatiivinen 548 (94,81 %), positiivinen kahdessa n\u00e4ytteess\u00e4 (0,35 %) ja ep\u00e4selv\u00e4 28 (4,84 %) n\u00e4ytteess\u00e4. Positiiviset IHK-tulokset olivat positiivisia FISH:ssa tai toisen sukupolven sekvensoinnissa ja ep\u00e4selv\u00e4t IHK-tulokset olivat negatiivisia FISH:ssa. ROS1-uudelleenj\u00e4rjest\u00e4ytymien esiintyvyys oli odotettua pienempi (0,35 %, adenokarsinoomissa 0,63). ROS1-IHK:n herkkyys (100 %) ja tarkkuus (96 %) vastasivat hyvin aiempia tuloksia. 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spellingShingle Tynkkynen, Niko ROS1 gene rearrangements in non-small cell lung cancer : immunohistochemistry and fluorescence in situ hybridization molecular diagnostics tyrosine kinase Solu- ja molekyylibiologia Cell and molecular biology 4013 translokaatio syöpätaudit keuhkosyöpä geenit adenokarsinooma syöpäsolut okasolusyöpä immunohistokemia histologia translocation (genetics) cancerous diseases pulmonary cancer genes adenocarcinoma cancer cells squamous cell carcinoma immunohistochemistry histology
title ROS1 gene rearrangements in non-small cell lung cancer : immunohistochemistry and fluorescence in situ hybridization
title_full ROS1 gene rearrangements in non-small cell lung cancer : immunohistochemistry and fluorescence in situ hybridization
title_fullStr ROS1 gene rearrangements in non-small cell lung cancer : immunohistochemistry and fluorescence in situ hybridization ROS1 gene rearrangements in non-small cell lung cancer : immunohistochemistry and fluorescence in situ hybridization
title_full_unstemmed ROS1 gene rearrangements in non-small cell lung cancer : immunohistochemistry and fluorescence in situ hybridization ROS1 gene rearrangements in non-small cell lung cancer : immunohistochemistry and fluorescence in situ hybridization
title_short ROS1 gene rearrangements in non-small cell lung cancer
title_sort ros1 gene rearrangements in non small cell lung cancer immunohistochemistry and fluorescence in situ hybridization
title_sub immunohistochemistry and fluorescence in situ hybridization
title_txtP ROS1 gene rearrangements in non-small cell lung cancer : immunohistochemistry and fluorescence in situ hybridization
topic molecular diagnostics tyrosine kinase Solu- ja molekyylibiologia Cell and molecular biology 4013 translokaatio syöpätaudit keuhkosyöpä geenit adenokarsinooma syöpäsolut okasolusyöpä immunohistokemia histologia translocation (genetics) cancerous diseases pulmonary cancer genes adenocarcinoma cancer cells squamous cell carcinoma immunohistochemistry histology
topic_facet 4013 Cell and molecular biology Solu- ja molekyylibiologia adenocarcinoma adenokarsinooma cancer cells cancerous diseases geenit genes histologia histology immunohistochemistry immunohistokemia keuhkosyöpä molecular diagnostics okasolusyöpä pulmonary cancer squamous cell carcinoma syöpäsolut syöpätaudit translocation (genetics) translokaatio tyrosine kinase
url https://jyx.jyu.fi/handle/123456789/75830 http://www.urn.fi/URN:NBN:fi:jyu-202105213091
work_keys_str_mv AT tynkkynenniko ros1generearrangementsinnonsmallcelllungcancerimmunohistochemistryandfluorescencei