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01-12-2013 | Translational Research and Biomarkers

Alteration of the E-cadherin/β-Catenin Complex Predicts Poor Response to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment

Authors: Seol Bong Yoo, MD, Yu Jung Kim, MD, Hyojin Kim, MD, Yan Jin, MD, Ping-Li Sun, MD, Sanghoon Jheon, MD, PhD, Jong Seok Lee, MD, PhD, Jin-Haeng Chung, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2013

Abstract

Background

Epidermal growth factor receptor (EGFR) mutation alone may be insufficient to predict clinical outcomes in the response to EGFR-tyrosine kinase inhibitor (TKI) therapy. The secondary mutation T790 M and MET amplification are mechanisms of acquired resistance to EGFR-TKI in approximately 50 % of patients, but the remaining mechanisms are unknown.

Methods

Eight metastatic lesions and specimens from 41 non-small cell lung carcinoma (NSCLC) patients harbouring activating EGFR mutations who underwent surgical resection and EGFR-TKI therapy were available. Immunohistochemistry was used to evaluate E-cadherin, β-catenin, and PTEN. Chromogenic in situ hybridisation and silver-enhanced in situ hybridisation were used to evaluate EGFR and MET amplification.

Results

Patients with E-cadherin/β-catenin alteration showed a poor objective response rate (ORR) (p = 0.005) and shorter overall survival (p = 0.059). Additionally, β-catenin alteration was associated with a poor ORR (p = 0.012). Of the metastatic tumours, three cases (37.5 %) showed the acquisition of altered E-cadherin/β-catenin and PTEN loss and two cases (25 %) demonstrated MET/EGFR amplification.

Conclusions

Altered E-cadherin/β-catenin expression in NSCLC harbouring EGFR mutations was associated with a poor response to EGFR-TKI. During metastatic progression, changes in E-cadherin/β-catenin were found. These results may suggest that E-cadherin/β-catenin alteration is related to poor TKI response and resistance.

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Title: Alteration of the E-cadherin/β-Catenin Complex Predicts Poor Response to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment
Authors: Seol Bong Yoo, MD
Yu Jung Kim, MD
Hyojin Kim, MD
Yan Jin, MD
Ping-Li Sun, MD
Sanghoon Jheon, MD, PhD
Jong Seok Lee, MD, PhD
Jin-Haeng Chung, MD, PhD
Publication date: 01-12-2013
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue Special Issue 3/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-013-2970-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Alteration of the E-cadherin/β-Catenin Complex Predicts Poor Response to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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