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Title: | EGFR and KRAS mutations do not enrich for the activation of IL-6, JAK1 or phosphorylated STAT3 in resected lung adenocarcinoma. | Austin 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 | Date: | 2017-09-06 | Publication information: | 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: | https://ahro.austin.org.au/austinjspui/handle/1/17956 | DOI: | 10.1007/s12032-017-1031-1 | ORCID: | 0000-0002-1953-2694 0000-0003-3414-112X |
Journal: | Medical oncology (Northwood, London, England) | PubMed URL: | 28879441 | Type: | Journal Article | Subjects: | EGFR mutation IL-6 JAK1 Lung adenocarcinoma pSTAT3 |
Appears in Collections: | Journal articles |
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