Annals of Surgical Oncology

, Volume 24, Issue 3, pp 770–777

Clinical Significance of C-MET Overexpression and Epidermal Growth Factor Receptor Mutation in Platinum-Based Adjuvant Chemotherapy Outcome in Surgically Resected Lung Adenocarcinoma

  • In-Ho Kim
  • In Hee Lee
  • Ji Eun Lee
  • Sook Hee Hong
  • Tae-Jung Kim
  • Kyo-Young Lee
  • Young Kyoon Kim
  • Seung Joon Kim
  • Sook Whan Sung
  • Jae Kil Park
  • Ie Ryung Yoo
  • Yeon Sil Kim
  • Jung-Oh Kim
  • Jin Hyoung Kang
Thoracic Oncology

DOI: 10.1245/s10434-016-5599-z

Cite this article as:
Kim, IH., Lee, I.H., Lee, J.E. et al. Ann Surg Oncol (2017) 24: 770. doi:10.1245/s10434-016-5599-z
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Abstract

Purpose

We retrospectively assessed the role of C-MET expression and epidermal growth factor receptor (EGFR) mutation on survival following platinum-based adjuvant chemotherapy. The impact of C-MET on survival was also investigated in relation to EGFR mutation status.

Methods

We enrolled 311 patients with resected lung adenocarcinoma (high-risk stage 1B–3A), and performed immunohistochemistry (IHC) using C-MET- and mutant EGFR (EGFRmut)-specific antibodies in tissue microarrays.

Results

Adjuvant chemotherapy was administered to 151 patients, 96 of whom relapsed and 85 died by the end of the study. On IHC, C-MET and EGFRmut were positive in 141 (45.3 %) and 88 (28.3 %) cases, respectively. On univariate analysis, adjuvant chemotherapy prolonged relapse-free survival (RFS) and overall survival (OS) in C-MET(+) patients (RFS p = 0.035; OS p = 0.013) but not in C-MET(−) patients. On multivariate analysis, adjuvant chemotherapy was a positive independent prognostic factor in C-MET(+) (RFS p = 0.013; OS p = 0.006) but not in C-MET(−) patients. In addition, univariate analysis showed no effect of EGFRmut status on RFS and OS after chemotherapy, whereas multivariate analysis revealed that adjuvant chemotherapy increased RFS in both EGFRmut(+) and EGFRmut(−) patients [EGFRmut(+) p = 0.033; EGFRmut(−) p = 0.030]. C-MET was a negative prognostic factor for RFS (p = 0.045) and OS (p = 0.007) in the EGFRmut(−) group but not in the EGFRmut(+) group, on multivariate analysis.

Conclusions

Our data indicate that patients with C-MET overexpression should be considered for adjuvant chemotherapy, and that C-MET negatively correlates with survival in patients with wild-type, but not mutant, EGFR.

Supplementary material

10434_2016_5599_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 17 kb)
10434_2016_5599_MOESM2_ESM.docx (36 kb)
Supplementary material 2 (DOCX 36 kb)

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • In-Ho Kim
    • 1
  • In Hee Lee
    • 1
  • Ji Eun Lee
    • 1
  • Sook Hee Hong
    • 1
    • 9
  • Tae-Jung Kim
    • 2
  • Kyo-Young Lee
    • 3
    • 9
  • Young Kyoon Kim
    • 4
    • 9
  • Seung Joon Kim
    • 4
    • 9
  • Sook Whan Sung
    • 5
    • 9
  • Jae Kil Park
    • 5
    • 9
  • Ie Ryung Yoo
    • 6
    • 9
  • Yeon Sil Kim
    • 7
    • 9
  • Jung-Oh Kim
    • 8
  • Jin Hyoung Kang
    • 1
    • 9
  1. 1.Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea
  2. 2.Department of Pathology, Yeouidol St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea
  3. 3.Department of Pathology, Seoul St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea
  4. 4.Department of Internal Medicine, Division of Pulmonology, Seoul St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea
  5. 5.Department of Thoracic Surgery, Seoul St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea
  6. 6.Department of Nuclear Medicine, Seoul St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea
  7. 7.Department of Radiation Oncology, Seoul St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea
  8. 8.Department of Biomedical SciencesThe Catholic University of KoreaSeoulKorea
  9. 9.Multidisciplinary Team of Lung Cancer of Seoul St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea