Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients

Kolmoisnegatiivinen rintasyöpä (TNBC) kattaa 10–15 % kaikista rintasyövistä. TNBC:ssä kasvaimen soluissa ei ole hormonireseptoreita eikä HER2-onkogeeni ole monistunut, sairaus etenee nopeasti ja hoitovaihtoehtoja on vähän. Tämän takia TNBC:n ennuste on huono. Ensimmäinen immunologinen lääkevalmiste...

Full description

Bibliographic Details
Main Author: Lehto, Niina
Other Authors: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Format: Master's thesis
Language:eng
Published: 2020
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/73209
_version_ 1826225725727834112
author Lehto, Niina
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Lehto, Niina Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Lehto, Niina Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Lehto, Niina
datasource_str_mv jyx
description Kolmoisnegatiivinen rintasyöpä (TNBC) kattaa 10–15 % kaikista rintasyövistä. TNBC:ssä kasvaimen soluissa ei ole hormonireseptoreita eikä HER2-onkogeeni ole monistunut, sairaus etenee nopeasti ja hoitovaihtoehtoja on vähän. Tämän takia TNBC:n ennuste on huono. Ensimmäinen immunologinen lääkevalmiste on hiljattain hyväksytty PD-L1-positiivisen TNBC:n hoitoon. Lääke inhiboi PD-1/PDL1 reittiä ja on parantanut huomattavasti TNBC-potilaiden selviytymistä. Kliiniseen käyttöön on hyväksytty myös immunohistokemiallinen (IHC) menetelmä, Ventana SP142, jonka avulla voidaan löytää tästä hoidosta mahdollisesti hyötyvät PD-L1- positiiviset TNBC-potilaat. Tässä työssä vertasimme kahta laboratoriossa kehitettyä PD-L1 IHC-menetelmää kaupalliseen Ventana SP142 menetelmään. Määritimme myös kasvainnäytteistä T-lymfosyyttien ja makrofagien määrän sekä selvitimme QuPath-sovelluksen mahdollisuuksia PD-L1:n määrittämisessä. Aineistoon kuului 113 TNBC-potilaan kasvainnäytettä Keski-Suomen Biopankista. Selvitimme myös PD-L1-positiivisuuden ja tulehdussolumäärien ennustemerkitystä TNBC-potilailla. Huomasimme, että tulehdussolujen PD-L1-positiivisuus erosi merkittävästi menetelmien välillä. Visuaalisen ja digitaalisen analyysin tulokset poikkesivat myös toisistaan. Tulehdussolujen suuri määrä oli yhteydessä TNBC-potilaiden parempaan ennusteeseen mutta PD-L1-positiivisuudella ei ollut vaikutusta. Standardin IHC-menetelmän määrittäminen sekä hoidon spesifi kohdentaminen TNBC-potilailla vaatii lisää tutkimusta. Triple-negative breast cancer (TNBC) accounts for 10-15% of all breast cancers. TNBC is negative for estrogen receptors, progesterone receptors, and the HER2 gene is not amplificated, grows fast but has only limited treatment options. Therefore, the prognosis of TNBC is poor. The first immunotherapy medicine has recently been approved to treat PD-L1-positive TNBC. This drug has remarkably improved TNBC patient's survival inhibiting the PD-1/PD-L1 pathway that cancer utilizes. For selecting TNBC patients to receive this treatment, an immunohistochemical (IHC) method, Ventana SP142, has been approved for clinical use to detect PD-L1- positivity. In this study, we compared PD-L1 expression in immune cells between two laboratory developed PD-L1 IHC protocols and companion Ventana SP142, detected the densities of T-lymphocytes and macrophages in tumor samples and tested the suitability of QuPath software for PD-L1 detection. The study material included tumor samples of 113 TNBC patients obtained from the Central Finland Biobank. Finally, we investigated the prognostic impact of PD-L1-positivity and immune cell densities in TNBC patients. PD-L1-positivity in immune cells differed significantly between the protocols as well as between visual and digital analysis. PD-L1-positivity did not associate with the patient's prognosis. However, high densities of immune cells were associated with better prognosis. The determination of a standard IHC method as well as the specific targeting of treatment in TNBC patients require further investigation.
first_indexed 2020-12-15T21:04:19Z
format Pro gradu
fullrecord [{"key": "dc.contributor.advisor", "value": "Kuopio, Teijo", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Ahtiainen, Maarit", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Lehto, Niina", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2020-12-15T09:36:00Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2020-12-15T09:36:00Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2020", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/73209", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Kolmoisnegatiivinen rintasy\u00f6p\u00e4 (TNBC) kattaa 10\u201315 % kaikista rintasy\u00f6vist\u00e4.\nTNBC:ss\u00e4 kasvaimen soluissa ei ole hormonireseptoreita eik\u00e4 HER2-onkogeeni ole\nmonistunut, sairaus etenee nopeasti ja hoitovaihtoehtoja on v\u00e4h\u00e4n. T\u00e4m\u00e4n takia\nTNBC:n ennuste on huono. Ensimm\u00e4inen immunologinen l\u00e4\u00e4kevalmiste on\nhiljattain hyv\u00e4ksytty PD-L1-positiivisen TNBC:n hoitoon. L\u00e4\u00e4ke inhiboi PD-1/PDL1 reitti\u00e4 ja on parantanut huomattavasti TNBC-potilaiden selviytymist\u00e4. Kliiniseen\nk\u00e4ytt\u00f6\u00f6n on hyv\u00e4ksytty my\u00f6s immunohistokemiallinen (IHC) menetelm\u00e4, Ventana\nSP142, jonka avulla voidaan l\u00f6yt\u00e4\u00e4 t\u00e4st\u00e4 hoidosta mahdollisesti hy\u00f6tyv\u00e4t PD-L1-\npositiiviset TNBC-potilaat. T\u00e4ss\u00e4 ty\u00f6ss\u00e4 vertasimme kahta laboratoriossa kehitetty\u00e4\nPD-L1 IHC-menetelm\u00e4\u00e4 kaupalliseen Ventana SP142 menetelm\u00e4\u00e4n. M\u00e4\u00e4ritimme\nmy\u00f6s kasvainn\u00e4ytteist\u00e4 T-lymfosyyttien ja makrofagien m\u00e4\u00e4r\u00e4n sek\u00e4 selvitimme\nQuPath-sovelluksen mahdollisuuksia PD-L1:n m\u00e4\u00e4ritt\u00e4misess\u00e4. Aineistoon kuului\n113 TNBC-potilaan kasvainn\u00e4ytett\u00e4 Keski-Suomen Biopankista. Selvitimme my\u00f6s\nPD-L1-positiivisuuden ja tulehdussolum\u00e4\u00e4rien ennustemerkityst\u00e4 TNBC-potilailla.\nHuomasimme, ett\u00e4 tulehdussolujen PD-L1-positiivisuus erosi merkitt\u00e4v\u00e4sti\nmenetelmien v\u00e4lill\u00e4. Visuaalisen ja digitaalisen analyysin tulokset poikkesivat my\u00f6s\ntoisistaan. Tulehdussolujen suuri m\u00e4\u00e4r\u00e4 oli yhteydess\u00e4 TNBC-potilaiden\nparempaan ennusteeseen mutta PD-L1-positiivisuudella ei ollut vaikutusta.\nStandardin IHC-menetelm\u00e4n m\u00e4\u00e4ritt\u00e4minen sek\u00e4 hoidon spesifi kohdentaminen\nTNBC-potilailla vaatii lis\u00e4\u00e4 tutkimusta.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Triple-negative breast cancer (TNBC) accounts for 10-15% of all breast cancers.\nTNBC is negative for estrogen receptors, progesterone receptors, and the HER2 gene\nis not amplificated, grows fast but has only limited treatment options. Therefore,\nthe prognosis of TNBC is poor. The first immunotherapy medicine has recently been\napproved to treat PD-L1-positive TNBC. This drug has remarkably improved TNBC\npatient's survival inhibiting the PD-1/PD-L1 pathway that cancer utilizes. For\nselecting TNBC patients to receive this treatment, an immunohistochemical (IHC)\nmethod, Ventana SP142, has been approved for clinical use to detect PD-L1-\npositivity. In this study, we compared PD-L1 expression in immune cells between\ntwo laboratory developed PD-L1 IHC protocols and companion Ventana SP142,\ndetected the densities of T-lymphocytes and macrophages in tumor samples and\ntested the suitability of QuPath software for PD-L1 detection. The study material\nincluded tumor samples of 113 TNBC patients obtained from the Central Finland\nBiobank. Finally, we investigated the prognostic impact of PD-L1-positivity and\nimmune cell densities in TNBC patients. PD-L1-positivity in immune cells differed\nsignificantly between the protocols as well as between visual and digital analysis.\nPD-L1-positivity did not associate with the patient's prognosis. However, high\ndensities of immune cells were associated with better prognosis. The determination\nof a standard IHC method as well as the specific targeting of treatment in TNBC\npatients require further investigation.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Paivi Vuorio (paelvuor@jyu.fi) on 2020-12-15T09:36:00Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2020-12-15T09:36:00Z (GMT). No. of bitstreams: 0\n Previous issue date: 2020", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "52", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.title", "value": "Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202012157155", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "restrictedAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "rintasy\u00f6p\u00e4", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "rinnat", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "immuunij\u00e4rjestelm\u00e4", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "immunologia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "diagnostiikka", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "breast cancer", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "breasts", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "immune system", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "immunology", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "diagnostics", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.format.content", "value": "fulltext", "language": null, "element": "format", "qualifier": "content", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "The author has not given permission to make the work publicly available electronically. Therefore the material can be read only at the archival workstation at Jyv\u00e4skyl\u00e4 University Library (https://kirjasto.jyu.fi/en/workspaces/facilities).", "language": "en", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "Tekij\u00e4 ei ole antanut lupaa avoimeen julkaisuun, joten aineisto on luettavissa vain Jyv\u00e4skyl\u00e4n yliopiston kirjaston arkistoty\u00f6semalta. Ks. https://kirjasto.jyu.fi/fi/tyoskentelytilat/laitteet-ja-tilat..", "language": "fi", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
id jyx.123456789_73209
language eng
last_indexed 2025-02-18T10:56:00Z
main_date 2020-01-01T00:00:00Z
main_date_str 2020
publishDate 2020
record_format qdc
source_str_mv jyx
spellingShingle Lehto, Niina Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients Solu- ja molekyylibiologia Cell and molecular biology 4013 rintasyöpä rinnat immuunijärjestelmä immunologia diagnostiikka breast cancer breasts immune system immunology diagnostics
title Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients
title_full Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients
title_fullStr Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients
title_full_unstemmed Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients
title_short Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients
title_sort comparison of two laboratory developed pd l1 assays with clinically approved ventana sp142 assay and prognostic significance of pd l1 positivity and immune cell densities in triple negative breast cancer patients
title_txtP Comparison of two laboratory developed PD-L1 assays with clinically approved Ventana SP142 assay and prognostic significance of PD-L1-positivity and immune cell densities in triple-negative breast cancer patients
topic Solu- ja molekyylibiologia Cell and molecular biology 4013 rintasyöpä rinnat immuunijärjestelmä immunologia diagnostiikka breast cancer breasts immune system immunology diagnostics
topic_facet 4013 Cell and molecular biology Solu- ja molekyylibiologia breast cancer breasts diagnostics diagnostiikka immune system immunologia immunology immuunijärjestelmä rinnat rintasyöpä
url https://jyx.jyu.fi/handle/123456789/73209 http://www.urn.fi/URN:NBN:fi:jyu-202012157155
work_keys_str_mv AT lehtoniina comparisonoftwolaboratorydevelopedpdl1assayswithclinicallyapprovedventanasp142assayan