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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Acknowledgment

This work was supported by the Korea Healthcare Technology R&D project, Ministry of Health & Welfare, Republic of Korea [A111405].

Disclosure

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

    Seol Bong Yoo MD, Hyojin Kim MD, Yan Jin MD, Ping-Li Sun MD & Jin-Haeng Chung MD, PhD

  2. Department of Pathology, Presbyterian Medical Center, Jeonju, Republic of Korea

    Seol Bong Yoo MD

  3. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

    Yu Jung Kim MD & Jong Seok Lee MD, PhD

  4. Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

    Ping-Li Sun MD & Sanghoon Jheon MD, PhD

Authors
  1. Seol Bong Yoo MD
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  2. Yu Jung Kim MD
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  3. Hyojin Kim MD
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  4. Yan Jin MD
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  6. Sanghoon Jheon MD, PhD
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  7. Jong Seok Lee MD, PhD
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Corresponding author

Correspondence to Jin-Haeng Chung MD, PhD.

Additional information

Seol Bong Yoo and Yu Jung Kim contributed equally to this article.

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Yoo, S.B., Kim, Y.J., Kim, H. et al. Alteration of the E-cadherin/β-Catenin Complex Predicts Poor Response to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment. Ann Surg Oncol 20 (Suppl 3), 545–552 (2013). https://doi.org/10.1245/s10434-013-2970-1

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  • DOI: https://doi.org/10.1245/s10434-013-2970-1

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