Journal of Pathology and Translational Medicine

Original Articles

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: Ji Ae Lee, Hye Eun Park, Seung-Yeon Yoo, Seorin Jeong, Nam-Yun Cho, Gyeong Hoon Kang, Jung Ho Kim; J Pathol Transl Med. 2019;53(4):225-235. Published online March 19, 2019; DOI: https://doi.org/10.4132/jptm.2019.03.12

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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.

Citations

Citations to this article as recorded by

Serrated Colorectal Lesions: An Up-to-Date Review from Histological Pattern to Molecular Pathogenesis
Martino Mezzapesa, Giuseppe Losurdo, Francesca Celiberto, Salvatore Rizzi, Antonio d’Amati, Domenico Piscitelli, Enzo Ierardi, Alfredo Di Leo
International Journal of Molecular Sciences.2022; 23(8): 4461. CrossRef
NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions
Jung Ho Kim, Jeong Hoon Hong, Yoon‐La Choi, Ji Ae Lee, Mi‐kyoung Seo, Mi‐Sook Lee, Sung Bin An, Min Jung Sung, Nam‐Yun Cho, Sung‐Su Kim, Young Kee Shin, Sangwoo Kim, Gyeong Hoon Kang
The Journal of Pathology.2021; 255(4): 399. CrossRef
Evolving pathologic concepts of serrated lesions of the colorectum
Jung Ho Kim, Gyeong Hoon Kang
Journal of Pathology and Translational Medicine.2020; 54(4): 276. CrossRef

Multiplicity of Advanced T Category–Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma: Hye Eun Park, Seungyeon Yoo, Jeong Mo Bae, Seorin Jeong, Nam-Yun Cho, Gyeong Hoon Kang; J Pathol Transl Med. 2018;52(6):386-395. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.02

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Abstract PDF

Background
Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance.
Methods
Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC.
Results
SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151).
Conclusions
Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer’s tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

Citations

Citations to this article as recorded by

Reveal the Regulation Patterns of Prognosis-Related miRNAs and lncRNAs Across Solid Tumors in the Cancer Genome Atlas
Zuojing Yin, Qiming Wang, Xinmiao Yan, Lu Zhang, Kailin Tang, Zhiwei Cao, Tianyi Qiu
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Whole-Slide Image Analysis Reveals Quantitative Landscape of Tumor–Immune Microenvironment in Colorectal Cancers
Seung-Yeon Yoo, Hye Eun Park, Jung Ho Kim, Xianyu Wen, Seorin Jeong, Nam-Yun Cho, Hwang Gwan Gwon, Kwangsoo Kim, Hye Seung Lee, Seung-Yong Jeong, Kyu Joo Park, Sae-Won Han, Tae-You Kim, Jeong Mo Bae, Gyeong Hoon Kang
Clinical Cancer Research.2020; 26(4): 870. CrossRef

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