Tumor Biology

, Volume 36, Issue 12, pp 9813–9821 | Cite as

Clinical and prognostic value of MET gene copy number gain and chromosome 7 polysomy in primary colorectal cancer patients

  • An Na Seo
  • Kyoung Un Park
  • Gheeyoung Choe
  • Woo Ho Kim
  • Duck-Woo Kim
  • Sung-Bum Kang
  • Hye Seung Lee
Research Article

Abstract

We aimed to explore the clinical and prognostic influence of numeric alterations of MET gene copy number (GCN) and chromosome 7 (CEP7) CN in colorectal cancer (CRC) patients. MET GCN and CEP7 CN were investigated in tissue arrayed tumors from 170 CRC patients using silver in situ hybridization (SISH). MET GCN gain was defined as ≥4 copies of MET, and CEP7 polysomy was prespecified as ≥3 copies of CEP7. Additionally, MET messenger RNA (mRNA) transcription was evaluated using mRNA ISH and compared with MET GCN. MET GCN gain was observed in 14.7 % (25/170), which correlated with advanced stage (P = 0.037), presence of distant metastasis (P = 0.006), and short overall survival (OS) (P = 0.009). In contrast, CEP7 polysomy was found in 6.5 % (11/170), which was related to tumor location in the left colon (P = 0.027) and poor OS (P = 0.029). MET GCN positively correlated with CEP7 CN (R = 0.659, P < 0.001) and mRNA transcription (R = 0.239, P = 0.002). Of note, MET GCN gain and CEP7 polysomy were also associated with poor OS (P = 0.016 and P < 0.001, respectively) in stage II/III CRC patients (n = 123). In multivariate analysis, CEP7 polysomy was an independent prognostic factor for poor OS in all patients (P = 0.009; hazard ratio [HR], 2.220; 95 % confidence interval [CI], 1.233–3.997) and in stage II/III CRC patients (P < 0.001; HR, 20.781; 95 % CI, 4.600–93.882). MET GCN gain and CEP7 polysomy could predict a poor outcome in CRC patients, especially CEP7 polysomy has the most powerful prognostic impact in stage II/III CRC patients.

Keywords

Colorectal cancer MET Chromosome 7 Silver in situ hybridization Copy number gain 

Notes

Acknowledgments

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI14C1813).

Conflicts of interest

None

Supplementary material

13277_2015_3726_Fig3_ESM.gif (24 kb)
Fig. S1

Prognostic value of MET GCN and CEP7 CN status in 123 patients with stage II/III CRC. Kaplan-Meier survival curves of MET GCN gain (mean ≥4 MET copies/cell) for (A) overall survival (OS) and (B) progression-free survival (PFS). Kaplan-Meier survival curves of CEP7 polysomy (mean ≥3 CEP7 copies/cell) for (C) OS and (D) PFS (GIF 24 kb)

13277_2015_3726_MOESM1_ESM.tif (3.3 mb)
High resolution image (TIFF 3365 kb)
13277_2015_3726_MOESM2_ESM.docx (21 kb)
Supplementary Table S1 (DOCX 20 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • An Na Seo
    • 1
  • Kyoung Un Park
    • 2
  • Gheeyoung Choe
    • 3
    • 4
  • Woo Ho Kim
    • 4
  • Duck-Woo Kim
    • 5
  • Sung-Bum Kang
    • 5
  • Hye Seung Lee
    • 3
  1. 1.Department of Pathology, Kyungpook National University Medical CenterKyungpook National University School of MedicineDaeguRepublic of Korea
  2. 2.Department of Laboratory MedicineSeoul National University Bundang HospitalSeongnam-siRepublic of Korea
  3. 3.Department of PathologySeoul National University Bundang HospitalBundang-gu, Seongnam-siRepublic of Korea
  4. 4.Department of PathologySeoul National University College of MedicineSeoulRepublic of Korea
  5. 5.Department of SurgerySeoul National University Bundang HospitalSeongnam-siRepublic of Korea

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