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dc.contributor.authorSouthwood, M
dc.contributor.authorKrenz, T
dc.contributor.authorCant, N
dc.contributor.authorMaurya, M
dc.contributor.authorGazdova, J
dc.contributor.authorMaxwell, P
dc.contributor.authorMcGready, C
dc.contributor.authorMoseley, E
dc.contributor.authorHughes, S
dc.contributor.authorStewart, P
dc.contributor.authorSalto-Tellez, M
dc.contributor.authorGroelz, D
dc.contributor.authorRassl, D
dc.contributor.authorSTRATfix Consortium
dc.date.accessioned2020-08-27T13:16:09Z
dc.date.issued2020-01
dc.identifier.citationThe journal of pathology. Clinical research, 2020, 6 (1), pp. 40 - 54
dc.identifier.issn2056-4538
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4045
dc.identifier.eissn2056-4538
dc.identifier.doi10.1002/cjp2.145
dc.description.abstractWhilst adequate for most existing pathological tests, formalin is generally considered a poor DNA preservative and use of alternative fixatives may prove advantageous for molecular testing of tumour material; an increasingly common approach to identify targetable driver mutations in lung cancer patients. We collected paired PAXgene® tissue-fixed and formalin-fixed samples of block-sized tumour and lung parenchyma, Temno-needle core tumour biopsies and fine needle tumour aspirates (FNAs) from non-small cell lung cancer resection specimens. Traditionally processed formalin fixed paraffin wax embedded (FFPE) samples were compared to paired PAXgene® tissue fixed paraffin-embedded (PFPE) samples. We evaluated suitability for common laboratory tests (H&E staining and immunohistochemistry) and performance for downstream molecular investigations relevant to lung cancer, including RT-PCR and next generation DNA sequencing (NGS). Adequate and comparable H&E staining was seen in all sample types and nuclear staining was preferable in PAXgene® fixed Temno tumour biopsies and tumour FNA samples. Immunohistochemical staining was broadly comparable. PFPE samples enabled greater yields of less-fragmented DNA than FFPE comparators. PFPE samples were also superior for PCR and NGS performance, both in terms of quality control metrics and for variant calling. Critically we identified a greater number of genetic variants in the epidermal growth factor receptor gene when using PFPE samples and the Ingenuity® Variant Analysis pipeline. In summary, PFPE samples are adequate for histopathological diagnosis and suitable for the majority of existing laboratory tests. PAXgene® fixation is superior for DNA and RNA integrity, particularly in low-yield samples and facilitates improved NGS performance, including the detection of actionable lung cancer mutations for precision medicine in lung cancer samples.
dc.formatPrint-Electronic
dc.format.extent40 - 54
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectSTRATfix Consortium
dc.titleSystematic evaluation of PAXgene® tissue fixation for the histopathological and molecular study of lung cancer.
dc.typeJournal Article
dcterms.dateAccepted2019-09-13
rioxxterms.versionofrecord10.1002/cjp2.145
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfThe journal of pathology. Clinical research
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.publication-statusPublished
pubs.volume6
pubs.embargo.termsNot known
icr.researchteamIntegrated Pathologyen_US
dc.contributor.icrauthorSalto-Tellez, Manuelen


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