dc.contributor.author | Southwood, M | |
dc.contributor.author | Krenz, T | |
dc.contributor.author | Cant, N | |
dc.contributor.author | Maurya, M | |
dc.contributor.author | Gazdova, J | |
dc.contributor.author | Maxwell, P | |
dc.contributor.author | McGready, C | |
dc.contributor.author | Moseley, E | |
dc.contributor.author | Hughes, S | |
dc.contributor.author | Stewart, P | |
dc.contributor.author | Salto-Tellez, M | |
dc.contributor.author | Groelz, D | |
dc.contributor.author | Rassl, D | |
dc.contributor.author | STRATfix Consortium, | |
dc.date.accessioned | 2020-08-27T13:16:09Z | |
dc.date.issued | 2019-11-11 | |
dc.identifier.citation | The journal of pathology. Clinical research, 2020, 6 (1), pp. 40 - 54 | |
dc.identifier.issn | 2056-4538 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4045 | |
dc.identifier.eissn | 2056-4538 | |
dc.identifier.doi | 10.1002/cjp2.145 | |
dc.description.abstract | Whilst 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.format | Print-Electronic | |
dc.format.extent | 40 - 54 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | STRATfix Consortium | |
dc.title | Systematic evaluation of PAXgene® tissue fixation for the histopathological and molecular study of lung cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-09-13 | |
rioxxterms.versionofrecord | 10.1002/cjp2.145 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The journal of pathology. Clinical research | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 6 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Integrated Pathology | |
dc.contributor.icrauthor | Salto-Tellez, Manuel | |