title: Are clinicopathological features of colorectal cancers with methylation in half of CpG island methylator phenotype panel markers different from those of CpG island methylator phenotype-high colorectal cancers?
abstract: CpG island methylator phenotype (CIMP)-high (CIMP-H) colorectal cancer (CRC) is defined when a tumor shows methylation at greater than or equal to 60% of CIMP panel markers. Although CRCs with methylation at 50% of panel markers are classified as CIMP-low/CIMP-0 tumors, little is known regarding the clinicopathological and molecular features of CRCs with methylation at 4/8 panel markers (4/8 methylated markers) and whether they are akin to CIMP-H or CIMP-low/CIMP-0 CRCs in terms of their clinicopathological or molecular features. A total of 1164 cases of surgically resected CRC were analyzed for their methylation status in 8 CIMP panel markers, and the frequencies of various clinicopathological and molecular features were compared between CRCs with 0/8, 1/8 to 3/8, 4/8, and 5/8 to 8/8 methylated markers. CRCs with 4/8 methylated markers were closer to CRCs with 5/8 to 8/8 methylated markers in terms of sex distribution, mucin production, serration, nodal metastasis, CK7 expression, CK20 loss, and CDX2 loss frequencies and overall survival rate. CRCs with methylation at 4/8 markers were closer to CRCs with 1/8 to 3/8 methylated markers in terms of less frequent right colon location and poor differentiation. CRCs with 4/8 methylated markers showed the shortest overall survival time compared with CRCs with 0/8, 1/8 to 3/8, 4/8, or 5/8 to 8/8 methylated markers. In terms of clinicopathological and molecular features, CRCs with 4/8 methylated markers appeared to be closer to CIMP-H than to CIMP-low/CIMP-0 and would thus be better classified as CIMP-H if the CRCs require classification into either CIMP-H or CIMP-low/CIMP-0.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Electronic address: jeongmobae@gmail.com.
authors.forename: Jeong Mo
authors.initials: JM
authors.lastname: Bae
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Electronic address: songyyii@naver.com.
authors.forename: Ye-Young
authors.initials: YY
authors.lastname: Rhee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Electronic address: sonicker@naver.com.
authors.forename: Kyung Ju
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea. Electronic address: hyunwoo625@snu.ac.kr.
authors.forename: Xianyu
authors.initials: X
authors.lastname: Wen
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea. Electronic address: suky0215@naver.com.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Song
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea. Electronic address: chonamyun@hanmail.net.
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea. Electronic address: ghkang@snu.ac.kr.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018899:CpG Islands; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D016016:Proportional Hazards Models; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Colorectal cancer; CpG island methylator phenotype; DNA methylation; Marker; Prognosis