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Medical Oncology
Erschienen in: Medical Oncology 10/2017

01.10.2017 | Original Paper

EGFR and KRAS mutations do not enrich for the activation of IL-6, JAK1 or phosphorylated STAT3 in resected lung adenocarcinoma

verfasst von: Timothy D. Clay, Prudence A. Russell, Hongdo Do, Vijaya Sundararajan, Matthew Conron, Gavin M. Wright, Benjamin Solomon, Alexander Dobrovic, Sue-Anne McLachlan, Melissa M. Moore

Erschienen in: Medical Oncology | Ausgabe 10/2017

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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.
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Metadaten
Titel
EGFR and KRAS mutations do not enrich for the activation of IL-6, JAK1 or phosphorylated STAT3 in resected lung adenocarcinoma
verfasst von
Timothy D. Clay
Prudence A. Russell
Hongdo Do
Vijaya Sundararajan
Matthew Conron
Gavin M. Wright
Benjamin Solomon
Alexander Dobrovic
Sue-Anne McLachlan
Melissa M. Moore
Publikationsdatum
01.10.2017
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 10/2017
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-017-1031-1

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