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dc.contributor.authorYoussef, Gehad
dc.contributor.authorGillet, Cheryl
dc.contributor.authorAgbaje, Orunsola
dc.contributor.authorCrompton, Tessa
dc.contributor.authorMontano, Ximena
dc.date.accessioned2015-01-08T10:32:32Z
dc.date.available2015-01-08T10:32:32Z
dc.date.issued2014-03
dc.identifier.citationYoussef , G , Gillet , C , Agbaje , O , Crompton , T & Montano , X 2014 , ' Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression : A potential novel prognostic marker for breast cancer ' , Modern Pathology , vol. 27 , no. 3 , pp. 361-374 . https://doi.org/10.1038/modpathol.2013.129
dc.identifier.issn0893-3952
dc.identifier.otherPURE: 1301020
dc.identifier.otherPURE UUID: 0e633a9a-662a-4933-9a85-8318246e8499
dc.identifier.otherScopus: 84896696221
dc.identifier.urihttp://hdl.handle.net/2299/15129
dc.description.abstractWe have identified a ligand-independent mechanism whereby the tumor suppressor, TP53, induces nerve growth factor receptor, NTRK1, phosphorylation at Y674/Y675 (NTRK1-pY674/pY675), via the repression of the NTRK1-phosphatase, PTPN6. This results in suppression of breast cancer cell proliferation. In this investigation, we aimed to establish whether perturbation of the wild-type TP53-NTRK1-pY674/pY675-PTPN6 pathway has an impact on disease-free survival of breast cancer patients without neo-adjuvant treatment. A total of 308 tumor samples were stained for NTRK1, NTRK1-pY674/pY675, PTPN6, and TP53 expression. Association between expression levels and disease-free survival was determined by the univariate/multivariate and Kaplan–Meir methods of analysis. DNA from tumors was sequenced to identify mutant or wild-type TP53. Tumors expressing NTRK1-pY674/pY675 but with undetectable or low levels of PTPN6 and TP53 were associated with prolonged 5, 10, and 15 years’ disease-free survival by 48%, 36%, and 37%, respectively, in the multivariate analysis (P<0.05). A similar result was observed in tumors expressing wild-type TP53, NTRK1-pY674/pY675, and low or undetectable levels of PTPN6. Given that estrogen receptor-positive breast cancers encode wild-type TP53, we analyzed this expression pattern in these tumors. Multivariate analysis showed that it was significantly and independently predictive of prolonged survival by 66%, 70%, and 84%, respectively, (P<0.05). The Kaplan–Meir method demonstrated that NTRK1-pY674/pY675 together with undetectable or low levels of PTPN6 correlated with 59% probability of disease-free survival (median survival 15 years), compared with 7% probability of disease-free survival (median survival 4.5 years) when absent. In luminal A tumors, the presence of this pattern was estimated to have a 61% probability of disease-free survival (median survival 15 years), compared with 6% probability of disease-free survival (median survival 3 years) when it was absent. These results strongly suggest that expression of NTRK1-pY674/pY675 together with wild-type TP53 and low levels of PTPN6 expression are predictors of improved disease-free survival and that they could be useful biomarkers to predict clinical outcome.en
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofModern Pathology
dc.titlePhosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression : A potential novel prognostic marker for breast canceren
dc.contributor.institutionDepartment of Allied Health Professions and Midwifery
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionParamedic Science
dc.contributor.institutionSchool of Health and Social Work
dc.contributor.institutionAllied Health Professions
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Health and Social Work
dcterms.dateAccepted2014-03
rioxxterms.versionofrecordhttps://doi.org/10.1038/modpathol.2013.129
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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