PMID- 27880934
OWN - NLM
STAT- MEDLINE
DCOM- 20180222
LR  - 20190920
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 52
DP  - 2016 Dec 27
TI  - Tumors with unmethylated MLH1 and the CpG island methylator phenotype are 
      associated with a poor prognosis in stage II colorectal cancer patients.
PG  - 86480-86489
LID - 10.18632/oncotarget.13441 [doi]
AB  - We previously developed a novel tumor subtype classification model for duodenal 
      adenocarcinomas based on a combination of the CpG island methylator phenotype 
      (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this 
      model in stage II colorectal cancer (CRC) patients. Tumors were assigned to 
      CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, 
      or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin 
      production differed among the four patient subgroups, and CIMP+/MLH1-U tumors 
      were more likely to have lymphovascular invasion and mucin production. 
      Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) 
      and overall survival (OS) among the four groups. In a multivariate analysis, 
      CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS 
      were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that 
      tumor subtype classification based on the combination of CIMP and MLH1 
      methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U 
      tumors exhibit aggressive features and are associated with poor clinical 
      outcomes.
FAU - Fu, Tao
AU  - Fu T
AD  - Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for 
      Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan 430060, China.
FAU - Liu, Yanliang
AU  - Liu Y
AD  - Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for 
      Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan 430060, China.
FAU - Li, Kai
AU  - Li K
AD  - Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for 
      Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan 430060, China.
FAU - Wan, Weiwei
AU  - Wan W
AD  - Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for 
      Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan 430060, China.
FAU - Pappou, Emmanouil P
AU  - Pappou EP
AD  - Department of Colon and Rectal Surgery, Columbia University Medical Center, New 
      York, NY 10032, USA.
FAU - Iacobuzio-Donahue, Christine A
AU  - Iacobuzio-Donahue CA
AD  - Department of Pathology and David Rubenstein Pancreatic Cancer Research Center, 
      Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
FAU - Kerner, Zachary
AU  - Kerner Z
AD  - Department of Surgery, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21287, USA.
FAU - Baylin, Stephen B
AU  - Baylin SB
AD  - Department of Oncology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21287, USA.
FAU - Wolfgang, Christopher L
AU  - Wolfgang CL
AD  - Department of Surgery, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21287, USA.
FAU - Ahuja, Nita
AU  - Ahuja N
AD  - Department of Surgery, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21287, USA.
AD  - Department of Oncology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21287, USA.
AD  - Department of Urology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD 21287, USA.
LA  - eng
GR  - K23 CA127141/CA/NCI NIH HHS/United States
GR  - R01 CA140599/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (MLH1 protein, human)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Colorectal Neoplasms/*genetics/mortality/pathology
MH  - *CpG Islands
MH  - *DNA Methylation
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - MutL Protein Homolog 1/*genetics
MH  - Neoplasm Staging
MH  - Phenotype
MH  - Prognosis
PMC - PMC5349928
OTO - NOTNLM
OT  - CpG island methylator phenotype
OT  - MLH1
OT  - colorectal cancer
OT  - methylation
OT  - prognosis
COIS- CONFLICTS OF INTEREST Stephen B. Baylin has commercial grant funding and serves 
      on the advisory board for MDx Health, Inc. and BioNumerik Pharmaceuticals, Inc. 
      Nita Ahuja has grant funding from Astex and has licensed biomarkers to Cepheid, 
      Inc. She has served as consultant for Ethicon. No potential conflicts of interest 
      were disclosed by the other authors.
EDAT- 2016/11/24 06:00
MHDA- 2018/02/23 06:00
PMCR- 2016/12/27
CRDT- 2016/11/24 06:00
PHST- 2016/08/02 00:00 [received]
PHST- 2016/11/09 00:00 [accepted]
PHST- 2016/11/24 06:00 [pubmed]
PHST- 2018/02/23 06:00 [medline]
PHST- 2016/11/24 06:00 [entrez]
PHST- 2016/12/27 00:00 [pmc-release]
AID - 13441 [pii]
AID - 10.18632/oncotarget.13441 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Dec 27;7(52):86480-86489. doi: 10.18632/oncotarget.13441.