Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17956
Title: EGFR and KRAS mutations do not enrich for the activation of IL-6, JAK1 or phosphorylated STAT3 in resected lung adenocarcinoma.
Authors: Clay, Timothy D;Russell, Prudence A;Do, Hongdo;Sundararajan, Vijaya;Conron, Matthew;Wright, Gavin M;Solomon, Benjamin;Dobrovic, Alexander;McLachlan, Sue-Anne;Moore, Melissa M
Affiliation: St John of God Hospital, Subiaco, Australia
Department of Medicine, St Vincent's Hospital, Melbourne Medical School, University of Melbourne, Melbourne, Australia
Department of Pathology, St Vincent's Hospital, Melbourne, Melbourne, Australia
Department of Pathology, University of Melbourne, Melbourne, Australia
Department of Respiratory Medicine, St Vincent's Hospital, Melbourne, Melbourne, Australia
Department of Thoracic Surgery, St Vincent's Hospital, Melbourne, Melbourne, Australia
Department of Thoracic Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
Department of Surgery, University of Melbourne, Melbourne, Australia
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Australia
Department of Medical Oncology, St Vincent's Hospital, Melbourne, Melbourne, Australia
Issue Date: 6-Sep-2017
EDate: 2017-09-06
Citation: Medical oncology (Northwood, London, England) 2017; 34(10): 175
Abstract: Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) against EGFR mutant lung adenocarcinoma develops after a median of nine to thirteen months. Upregulation of the interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway may be a potential source of resistance to EGFR TKIs. We undertook a detailed assessment of the IL-6/JAK1/phosphorylated STAT3 (pSTAT3) pathway in resected lung adenocarcinoma specimens, with special interest in whether the presence of an EGFR mutation enriched for pSTAT3 positivity. Tumours from 143 patients with resected lung adenocarcinoma were assessed. EGFR and KRAS mutation status were scanned for with high-resolution melting and confirmed by polymerase chain reaction. Immunohistochemisty (IHC) was performed for IL-6, gp130, JAK1 and pSTAT3. Two methods for assigning IHC positivity were assessed (the presence of any positivity, and the presence of positivity at an H score >40). We found statistically significant associations between IL-6, JAK1 and pSTAT3 measured by IHC, consistent with the activation of the pathway in clinical specimens. No relationship was demonstrated between members of this pathway and oncogenic mutations in EGFR or KRAS. However, a proportion of tumours with EGFR mutations showed staining for IL-6, JAK1 and pSTAT3. No correlations with clinicopathologic features or survival outcomes were found for IL-6, JAK1 or pSTAT3 staining. The presence of EGFR or KRAS mutations did not enrich for the activation of IL-6, JAK1 or pSTAT3. pSTAT3 may still play a role in resistance to EGFR TKIs in clinical practice.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17956
DOI: 10.1007/s12032-017-1031-1
ORCID: 0000-0002-1953-2694
0000-0003-3414-112X
PubMed URL: 28879441
Type: Journal Article
Subjects: EGFR mutation
IL-6
JAK1
Lung adenocarcinoma
pSTAT3
Appears in Collections:Journal articles

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