Field Cancerization in Sporadic Colon Cancer.
OBJECTIVE
Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2 ), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients.


METHODS
We investigated promoter methylation in 34 CRC patients and five individuals with normal colonoscopy results. CRC patients were divided into three tissue groups: tumor tissue, adjacent and nonadjacent normal-appearing tissue. The methylation status (positive: methylation level >20%) of SFRP2 , TFPI2 , NDRG4 , and BMP3 promoters was investigated using methylation-specific PCR.


RESULTS
The methylation frequencies of the SFRP2 , TFPI2 , NDRG4 and BMP3 promoters in tumor/adjacent/nonadjacent normal-appearing tissue were 79.4%/63.0%/70.4%, 82.4%/53.6%/60.7%, 76.5%/61.5%/69.2%, 41.2%/35.7%/50.0%, respectively. The methylation levels of the SFRP, TFPI2, NDRG4 and BMP3 promoters in tumor tissues were significantly higher than those in normal-appearing tissue (SFRP2, p=0.013; TFPI2, p<0.001; NDRG4, p=0.003; BMP3, p=0.001). No significant correlation was observed between the methylation levels of the promoters and the clinicopathological variables.


CONCLUSIONS
The field effect is present in CRC and affects both the adjacent and nonadjacent normal-appearing mucosa.
Division of Gastroentorology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Soo-Kyung
SK
Park
Division of Gastroentorology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chang Seok
CS
Song
Division of Gastroentorology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hyo-Joon
HJ
Yang
Division of Gastroentorology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yoon Suk
YS
Jung
Division of Gastroentorology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kyu Yong
KY
Choi
Division of Gastroentorology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Dong Hoe
DH
Koo
Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kyung Eun
KE
Kim
Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kyung Uk
KU
Jeong
Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hyung Ook
HO
Kim
Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hungdai
H
Kim
Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ho-Kyung
HK
Chun
Division of Gastroentorology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.|Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Dong Il
DI
Park
D014408:Biomarkers, Tumor / Q000235:genetics*; D055398:Bone Morphogenetic Protein 3 / Q000235:genetics; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D003113:Colonoscopy; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000094742:Secreted Frizzled-Related Proteins
D014408:Biomarkers, Tumor; D055398:Bone Morphogenetic Protein 3; D052006:Bone Morphogenetic Protein Receptors, Type II; D006023:Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C431705:NDRG4 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C021240:tissue-factor-pathway inhibitor 2; C498218:BMPR2 protein, human
Colorectal neoplasms; DNA methylation; Epigenomics; Field effect