Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16618
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dc.contributor.authorAmeratunga, Malaka-
dc.contributor.authorAsadi, Khashayar-
dc.contributor.authorLin, Xihui-
dc.contributor.authorWalkiewicz, Marzena-
dc.contributor.authorMurone, Carmel-
dc.contributor.authorKnight, Simon-
dc.contributor.authorMitchell, Paul L R-
dc.contributor.authorBoutros, Paul-
dc.contributor.authorJohn, Thomas-
dc.date2017-04-22-
dc.date.accessioned2017-04-24T00:28:45Z-
dc.date.available2017-04-24T00:28:45Z-
dc.date.issued2017-04-22-
dc.identifier.citationPLoS One 2017: 11(4): e0153954en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/16618-
dc.description.abstractINTRODUCTION: Immune checkpoint inhibition has shifted treatment paradigms in non-small cell lung cancer (NSCLC). Conflicting results have been reported regarding the immune infiltrate and programmed death-ligand 1 (PD-L1) as a prognostic marker. We correlated the immune infiltrate and PD-L1 expression with clinicopathologic characteristics in a cohort of resected NSCLC. METHODS: A tissue microarray was constructed using triplicate cores from consecutive resected NSCLC. Immunohistochemistry was performed for CD8, FOXP3 and PD-L1. Strong PD-L1 expression was predefined as greater than 50% tumor cell positivity. Matched nodal samples were assessed for concordance of PD-L1 expression. RESULTS: Of 522 patients, 346 were node-negative (N0), 72 N1 and 109 N2; 265 were adenocarcinomas (AC), 182 squamous cell cancers (SCC) and 75 other. Strong PD-L1 expression was found in 24% cases. In the overall cohort, PD-L1 expression was not associated with survival. In patients with N2 disease, strong PD-L1 expression was associated with significantly improved disease-free (DFS) and overall survival (OS) in multivariate analysis (HR 0.49, 95%CI 0.36-0.94, p = 0.031; HR 0.46, 95%CI 0.26-0.80, p = 0.006). In this resected cohort only 5% harboured EGFR mutations, whereas 19% harboured KRAS and 23% other. KRAS mutated tumors were more likely to highly express PD-L1 compared to EGFR (22% vs 3%). A stromal CD8 infiltrate was associated with significantly improved DFS in SCC (HR 0.70, 95%CI 0.50-0.97, p = 0.034), but not AC, whereas FOXP3 was not prognostic. Matched nodal specimens (N = 53) were highly concordant for PD-L1 expression (89%). CONCLUSION: PD-L1 expression was not prognostic in the overall cohort. PD-L1 expression in primary tumor and matched nodal specimens were highly concordant. The observed survival benefit in N2 disease requires confirmation.en
dc.subjectLung neoplasmsen
dc.subjectLymphocytes, tumor-infiltratingen
dc.subjectBiomarkers, tumoren
dc.subjectAntigens, CD274en
dc.titlePD-L1 and tumor infiltrating lymphocytes as prognostic markers in resected NSCLCen
dc.typeJournal Articleen
dc.identifier.journaltitlePLoS Oneen
dc.identifier.affiliationDepartment of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Pathology, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationInformatics & Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Canadaen
dc.identifier.affiliationThe Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Thoracics, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medical Biophysics, University of Toronto, Toronto, Canadaen
dc.identifier.affiliationDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, Canadaen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Victoria, Australiaen
dc.identifier.affiliationUniversity of Melbourne, Melbourne, Victoria, Australiaen
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/27104612en
dc.identifier.doi10.1371/journal.pone.0153954en
dc.type.contentTexten
dc.type.austinJournal Articleen_US
local.name.researcherAsadi, Khashayar
item.openairetypeJournal Article-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.fulltextNo Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.author.deptPathology-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
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