Adverse prognostic impact of the CpG island methylator phenotype in metastatic colorectal cancer.
The association between the CpG island methylator phenotype (CIMP) and clinical outcomes in metastatic colorectal cancer remains unclear. We investigated the prognostic impact of CIMP in patients with metastatic colorectal cancer treated with systemic chemotherapy.



Eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, CDKN2A, CRABP1, and MLH1) were examined. The CIMP status was determined by the number of methylated promoters as high (⩾5), low (1-4), and negative (0).



A total of 153 patients were included (men/women, 103/50; median age, 61 years; range, 22-80 years). The CIMP status was negative/low/high in 77/ 69/7 patients, respectively. Overall survival (OS) was significantly different among the three CIMP groups, with median values of 35.7, 22.2, and 9.77 months for the negative, low, and high groups, respectively (P<0.001). For patients treated with fluoropyrimidine and oxaliplatin first-line chemotherapy (N=128), OS and progression-free survival (PFS) were significantly different among the three CIMP groups; the median OS was 37.9, 23.8, and 6.77 months for the negative, low, and high groups, respectively (P<0.001), while the median PFS was 9.97, 7.87, and 1.83 months, respectively (P=0.002). Response rates were marginally different among the three CIMP groups (53.4% vs 45.1% vs 16.7%, respectively; P=0.107). For patients treated with fluoropyrimidine and irinotecan second-line chemotherapy (N=86), only OS showed a difference according to the CIMP status, with median values of 20.4, 13.4, and 2.90 months for the negative, low, and high groups, respectively (P<0.001).



The CIMP status is a negative prognostic factor for patients with metastatic colorectal cancer treated with chemotherapy.
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Yongjun
Y
Cha
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Kyung-Ju
KJ
Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Sae-Won
SW
Han
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Ye Young
YY
Rhee
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Jeong Mo
JM
Bae
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Xianyu
X
Wen
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Nam-Yun
NY
Cho
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Dae-Won
DW
Lee
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Kyung-Hun
KH
Lee
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Tae-Yong
TY
Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Do-Youn
DY
Oh
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Seock-Ah
SA
Im
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Yung-Jue
YJ
Bang
Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
Seung-Yong
SY
Jeong
Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
Kyu Joo
KJ
Park
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Gyeong Hoon
GH
Kang
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea.
Tae-You
TY
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010641:Phenotype; D011379:Prognosis; D055815:Young Adult
D000970:Antineoplastic Agents