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dc.contributor.authorLeal, MF
dc.contributor.authorHaynes, BP
dc.contributor.authorMacNeill, FA
dc.contributor.authorDodson, A
dc.contributor.authorDowsett, M
dc.date.accessioned2019-03-26T16:03:22Z
dc.date.issued2019-06
dc.identifier.citationBreast cancer research and treatment, 2019, 175 (2), pp. 317 - 326
dc.identifier.issn0167-6806
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3165
dc.identifier.eissn1573-7217
dc.identifier.doi10.1007/s10549-019-05163-6
dc.description.abstractPurpose We evaluated whether multiplex protein quantification using antibody bar-coding with photocleavable oligonucleotides (NanoString) can be applied to evaluate protein expression in breast cancer FFPE specimens. We also assessed whether diagnostic core-cuts fixed immediately at time of procedures and surgical excision sections from routinely fixed breast cancers are affected by the same fixation related differences noted using immunohistochemistry (IHC).Methods The expression of 26 proteins was analysed using NanoString technology in 16 pairs of FFPE breast cancer core-cuts and surgical excisions. The measurements yielded were compared with those by IHC on Ki67, PgR and HER2 biomarkers and pAKT and pERK1/2 phosphorylated proteins.Results When considered irrespective of sample type, expression measured by the two methods was strongly correlated for all markers (p < 0.001; ρ = 0.69-0.88). When core-cuts and excisions were evaluated separately, the correlations between NanoString and IHC were weaker but significant except for pAKT in excisions. Surgical excisions showed lower levels of 8/12 phosphoproteins and higher levels of 4/13 non-phosphorylated proteins in comparison to core-cuts (p < 0.01). Reduced p4EBP1, pAMPKa, pRPS6 and pRAF1 immunogenicity in excisions was correlated with tumour size and mastectomy specimens showed lower p4EBP1 and pRPS6 expression than lumpectomy (p < 0.05).Conclusions Our study supports the validity of the new multiplex approach to protein analysis but indicates that, as with IHC, caution is necessary for the analysis in excisions particularly of phosphoproteins. The specimen type, tumour size and surgery type may lead to biases in the quantitative analysis of many proteins of biologic and clinical interest in excision specimens.
dc.formatPrint-Electronic
dc.format.extent317 - 326
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectFormaldehyde
dc.subjectProtein Kinases
dc.subjectProto-Oncogene Proteins c-raf
dc.subjectReceptor, erbB-2
dc.subjectNeoplasm Proteins
dc.subjectKi-67 Antigen
dc.subjectReceptors, Progesterone
dc.subjectMastectomy
dc.subjectImmunohistochemistry
dc.subjectParaffin Embedding
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectBiopsy, Large-Core Needle
dc.subjectBiomarkers, Tumor
dc.titleComparison of protein expression between formalin-fixed core-cut biopsies and surgical excision specimens using a novel multiplex approach.
dc.typeJournal Article
dcterms.dateAccepted2019-02-06
rioxxterms.versionofrecord10.1007/s10549-019-05163-6
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBreast cancer research and treatment
pubs.issue2
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.publication-statusPublished
pubs.volume175
pubs.embargo.termsNot known
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorDowsett, Mitch


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