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CpG Island Methylation in Sessile Serrated Adenoma/Polyp of the Colorectum: Implications for Differential Diagnosis of Molecularly High-Risk Lesions among Non-dysplastic Sessile Serrated Adenomas/Polyps.
Lee, Ji Ae; Park, Hye Eun; Yoo, Seung-Yeon; Jeong, Seorin; Cho, Nam-Yun; Kang, Gyeong Hoon; Kim, Jung Ho.
Affiliation
  • Lee JA; Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • Park HE; Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • Yoo SY; Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • Jeong S; Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • Cho NY; Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • Kang GH; Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • Kim JH; Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
J Pathol Transl Med ; 53(4): 225-235, 2019 Jul.
Article in En | MEDLINE | ID: mdl-30887794
BACKGROUND: Although colorectal sessile serrated adenomas/polyps (SSA/Ps) with morphologic dysplasia are regarded as definite high-risk premalignant lesions, no reliable grading or risk-stratifying system exists for non-dysplastic SSA/Ps. The accumulation of CpG island methylation is a molecular hallmark of progression of SSA/Ps. Thus, we decided to classify non-dysplastic SSA/Ps into risk subgroups based on the extent of CpG island methylation. METHODS: The CpG island methylator phenotype (CIMP) status of 132 non-dysplastic SSA/Ps was determined using eight CIMP-specific promoter markers. SSA/Ps with CIMP-high and/or MLH1 promoter methylation were regarded as a high-risk subgroup. RESULTS: Based on the CIMP analysis results, methylation frequency of each CIMP marker suggested a sequential pattern of CpG island methylation during progression of SSA/P, indicating MLH1 as a late-methylated marker. Among the 132 non-dysplastic SSA/Ps, 34 (26%) were determined to be high-risk lesions (33 CIMP-high and 8 MLH1-methylated cases; seven cases overlapped). All 34 high-risk SSA/Ps were located exclusively in the proximal colon (100%, p = .001) and were significantly associated with older age (≥ 50 years, 100%; p = .003) and a larger histologically measured lesion size (> 5 mm, 100%; p = .004). In addition, the high-risk SSA/Ps were characterized by a relatively higher number of typical base-dilated serrated crypts. CONCLUSIONS: Both CIMP-high and MLH1 methylation are late-step molecular events during progression of SSA/Ps and rarely occur in SSA/Ps of young patients. Comprehensive consideration of age (≥ 50), location (proximal colon), and histologic size (> 5 mm) may be important for the prediction of high-risk lesions among non-dysplastic SSA/Ps.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Language: En Journal: J Pathol Transl Med Year: 2019 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Language: En Journal: J Pathol Transl Med Year: 2019 Document type: Article Country of publication: