Clinical and prognostic value of MET gene copy number gain and chromosome 7 polysomy in primary colorectal cancer patients
- 171 Downloads
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.
KeywordsColorectal cancer MET Chromosome 7 Silver in situ hybridization Copy number gain
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
- 3.Hari DM, Leung AM, Lee JH, Sim MS, Vuong B, Chiu CG, et al. AJCC cancer staging manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg. 2013;217(2):181–90. doi: 10.1016/j.jamcollsurg.2013.04.018.CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Cappuzzo F, Marchetti A, Skokan M, Rossi E, Gajapathy S, Felicioni L, et al. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol. 2009;27(10):1667–74. doi: 10.1200/jco.2008.19.1635.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Edge SB, Byrd DR, Compton C, Fritz A, Greene F, Trotti A. American joint committee on cancer staging manual. American Joint Committee on Cancer Staging Manual. 2010.Google Scholar
- 21.Kim MA, Jung JE, Lee HE, Yang HK, Kim WH. In situ analysis of HER2 mRNA in gastric carcinoma: comparison with fluorescence in situ hybridization, dual-color silver in situ hybridization, and immunohistochemistry. Hum Pathol. 2013;44(4):487–94. doi: 10.1016/j.humpath.2012.06.022.CrossRefPubMedGoogle Scholar
- 22.Choi J, Lee HE, Kim MA, Jang BG, Lee HS, Kim WH. Analysis of MET mRNA expression in gastric cancers using RNA in situ hybridization assay: its clinical implication and comparison with immunohistochemistry and silver in situ hybridization. PLoS One. 2014;9(11), e111658. doi: 10.1371/journal.pone.0111658.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Guo B, Cen H, Tan X, Liu W, Ke Q. Prognostic value of MET gene copy number and protein expression in patients with surgically resected non-small cell lung cancer: a meta-analysis of published literatures. PLoS One. 2014;9(6), e99399. doi: 10.1371/journal.pone.0099399.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Sheffer M, Bacolod MD, Zuk O, Giardina SF, Pincas H, Barany F, et al. Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer. Proc Natl Acad Sci U S A. 2009;106(17):7131–6. doi: 10.1073/pnas.0902232106.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Gordon MS, Sweeney CS, Mendelson DS, Eckhardt SG, Anderson A, Beaupre DM, et al. Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors. Clin Cancer Res. 2010;16(2):699–710. doi: 10.1158/1078-0432.ccr-09-1365.CrossRefPubMedGoogle Scholar
- 35.Garouniatis A, Zizi-Sermpetzoglou A, Rizos S, Kostakis A, Nikiteas N, Papavassiliou AG. FAK, CD44v6, c-Met and EGFR in colorectal cancer parameters: tumor progression, metastasis, patient survival and receptor crosstalk. Int J Color Dis. 2013;28(1):9–18. doi: 10.1007/s00384-012-1520-9.CrossRefGoogle Scholar
- 40.Li YH, Wang F, Shen L, Deng YM, Shao Q, Feng F, et al. EGFR fluorescence in situ hybridization pattern of chromosome 7 disomy predicts resistance to cetuximab in KRAS wild-type metastatic colorectal cancer patients. Clin Cancer Res. 2011;17(2):382–90. doi: 10.1158/1078-0432.ccr-10-0208.CrossRefPubMedGoogle Scholar