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c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer.

Lee KS, Kwak Y, Nam KH, Kim DW, Kang SB, Choe G, Kim WH, Lee HS - PLoS ONE (2015)

Bottom Line: 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).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).Our findings indicate that the status of c-MYC may be helpful in predicting the patients' outcome and for managing CRC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves illustrating the prognostic effect of c-MYC status in colorectal cancer (cohort 1).(A) c-MYC gene copy number (GCN) gain; (B) c-MYC GCN gain in the stage II-III subgroup; (C) c-MYC amplification.
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pone.0139727.g002: Kaplan-Meier survival curves illustrating the prognostic effect of c-MYC status in colorectal cancer (cohort 1).(A) c-MYC gene copy number (GCN) gain; (B) c-MYC GCN gain in the stage II-III subgroup; (C) c-MYC amplification.

Mentions: In consecutive primary CRC cases (cohort 1), the median c-MYC:CEP8 ratio was 1.29 (range, 0.58–5.17). c-MYC gene amplification, defined by a c-MYC:CEP8 ratio ≥ 2.0 and similar to that established for HER2 [20], was detected in 31 (8.4%) of 367 patients. The mean c-MYC GCN was 2.88 (range, 1.22–13.12). In the present study, we defined the GCN gain as ≥ 4.0 c-MYC copies/nucleus [21], and this was detected in 63 (17.2%) of 367 CRC patients. All c-MYC amplification was included in c-MYC GCN gain. A c-MYC GCN gain ≥ 4 had the lowest P-value (P = 0.015) and thus, was observed to be the most predictive cut-off point for patient prognosis (Fig 2); ≥ 5.0 c-MYC copies/nucleus also influenced patient prognosis (P = 0.026). There was no significant association between patient prognosis and either c-MYC amplification (P = 0.149) or > 2, ≥ 3, and ≥ 6 c-MYC copies/nucleus (P = 0.752, P = 0.175, and P = 0.122, respectively).


c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer.

Lee KS, Kwak Y, Nam KH, Kim DW, Kang SB, Choe G, Kim WH, Lee HS - PLoS ONE (2015)

Kaplan-Meier survival curves illustrating the prognostic effect of c-MYC status in colorectal cancer (cohort 1).(A) c-MYC gene copy number (GCN) gain; (B) c-MYC GCN gain in the stage II-III subgroup; (C) c-MYC amplification.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4591346&req=5

pone.0139727.g002: Kaplan-Meier survival curves illustrating the prognostic effect of c-MYC status in colorectal cancer (cohort 1).(A) c-MYC gene copy number (GCN) gain; (B) c-MYC GCN gain in the stage II-III subgroup; (C) c-MYC amplification.
Mentions: In consecutive primary CRC cases (cohort 1), the median c-MYC:CEP8 ratio was 1.29 (range, 0.58–5.17). c-MYC gene amplification, defined by a c-MYC:CEP8 ratio ≥ 2.0 and similar to that established for HER2 [20], was detected in 31 (8.4%) of 367 patients. The mean c-MYC GCN was 2.88 (range, 1.22–13.12). In the present study, we defined the GCN gain as ≥ 4.0 c-MYC copies/nucleus [21], and this was detected in 63 (17.2%) of 367 CRC patients. All c-MYC amplification was included in c-MYC GCN gain. A c-MYC GCN gain ≥ 4 had the lowest P-value (P = 0.015) and thus, was observed to be the most predictive cut-off point for patient prognosis (Fig 2); ≥ 5.0 c-MYC copies/nucleus also influenced patient prognosis (P = 0.026). There was no significant association between patient prognosis and either c-MYC amplification (P = 0.149) or > 2, ≥ 3, and ≥ 6 c-MYC copies/nucleus (P = 0.752, P = 0.175, and P = 0.122, respectively).

Bottom Line: 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).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).Our findings indicate that the status of c-MYC may be helpful in predicting the patients' outcome and for managing CRC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus