c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal CancerReportar como inadecuado




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Background

The aim of this study was to determine the incidence and clinicopathological significance of c-MYC gene copy-number GCN gain in patients with primary colorectal cancer CRC.

Methods

The c-MYC GCN was investigated in 367 consecutive CRC patients cohort 1 by using dual-color silver in situ hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC tissue from 3 sites including the primary cancer, distant metastasis, and lymph-node metastasis in 152 advanced CRC patients cohort 2. KRAS exons 2 and 3 were investigated for mutations.

Results

In cohort 1, c-MYC gene amplification, defined by a c-MYC:centromere of chromosome 8 ratio ≥ 2.0, was detected in 31 8.4% of 367 patients. A c-MYC GCN gain, defined by ≥ 4.0 c-MYC copies-nucleus, was found in 63 17.2% patients and was associated with poor prognosis P = 0.015. Multivariate Cox regression analysis showed that the hazard ratio for c-MYC GCN gain was 2.35 95% confidence interval, 1.453–3.802; P < 0.001. In a subgroup of stage II-III CRC patients, c-MYC GCN gain was significantly associated with poor prognosis by univariate P = 0.034 and multivariate P = 0.040 analyses. c-MYC protein overexpression was observed in 201 54.8% out of 367 patients and weakly correlated with c-MYC GCN gain ρ, 0.211. In cohort 2, the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance between GCN gain in the primary tumor and either distant or lymph-node metastasis was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and amplification was observed in CRC patients with both wild-type and mutated KRAS.

Conclusions

c-MYC GCN gain was an independent factor for poor prognosis in consecutive CRC patients and in the stage II-III subgroup. Our findings indicate that the status of c-MYC may be helpful in predicting the patients’ outcome and for managing CRC patients.



Autor: Kyu Sang Lee, Yoonjin Kwak, Kyung Han Nam, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee

Fuente: http://plos.srce.hr/



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