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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

Representative figures of c-MYC status detected by dual-color silver in situ hybridization (A and B) in colorectal cancer patients.(A) c-MYC gene copy number gain (60 × magnification); (B) c-MYC gene disomy (60 × magnification).
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pone.0139727.g001: Representative figures of c-MYC status detected by dual-color silver in situ hybridization (A and B) in colorectal cancer patients.(A) c-MYC gene copy number gain (60 × magnification); (B) c-MYC gene disomy (60 × magnification).

Mentions: The c-MYC gene was visualized by using a blue-staining system (ultraView silver in situ hybridization [SISH] dinitrophenol [DNP] detection kit and c-MYC DNP probe, Ventana Medical Systems, Tucson, AZ, USA). The centromere of chromosome 8 (CEP8) was visualized by using a red-staining system (ultraView red ISH digoxigenin [DIG] detection kit and chromosome 8 DIG probe, Ventana Medical Systems). Positive signals were visualized at 60 × magnification and counted in 50 non-overlapping tumor cell nuclei for each case (Fig 1) [17]. Small and large clusters were scored as 6 and 12 signals, 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)

Representative figures of c-MYC status detected by dual-color silver in situ hybridization (A and B) in colorectal cancer patients.(A) c-MYC gene copy number gain (60 × magnification); (B) c-MYC gene disomy (60 × magnification).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139727.g001: Representative figures of c-MYC status detected by dual-color silver in situ hybridization (A and B) in colorectal cancer patients.(A) c-MYC gene copy number gain (60 × magnification); (B) c-MYC gene disomy (60 × magnification).
Mentions: The c-MYC gene was visualized by using a blue-staining system (ultraView silver in situ hybridization [SISH] dinitrophenol [DNP] detection kit and c-MYC DNP probe, Ventana Medical Systems, Tucson, AZ, USA). The centromere of chromosome 8 (CEP8) was visualized by using a red-staining system (ultraView red ISH digoxigenin [DIG] detection kit and chromosome 8 DIG probe, Ventana Medical Systems). Positive signals were visualized at 60 × magnification and counted in 50 non-overlapping tumor cell nuclei for each case (Fig 1) [17]. Small and large clusters were scored as 6 and 12 signals, 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