DNA hypermethylation as a predictor of extramural vascular invasion (EMVI) in rectal cancer

Kokelaar, Rory; Jones, H; Williamson, John S.; Williams, Namor; Griffiths, Ann; Beynon, J.; Jenkins, Gareth; Harris, Dean

doi:10.1080/15384047.2017.1416933

Cited by 9 publications

(11 citation statements)

References 62 publications

(67 reference statements)

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“…CIMP-H tumors were also found to be associated with presence of Crohn-like infiltrate [OR = 2.89 (95% CI = 1.23-6.78, I 2 = 88.4%] in pooled analysis of four studies [44] , [69] , [100] , [101] . No associations were observed for CIMP status with vascular invasion [OR = 1.20 (95% CI = 0.77-1.88, I 2 = 35.7%)] across nine studies [45] , [52] , [65] , [69] , [71] , [72] , [77] , [83] , [104] . Finally, we also confirmed association of CIMP-H tumors with mucinous histology [OR = 2.60 (95% CI = 1.73-3.89, I 2 = 80.90%)] in pooled analysis of 21 studies [19] , [25] , [30] , [36] , [39] , [41] , [43] , [44] , [54] , [56] , [58] , [65] , [66] , [72] , [76] , [77] , [81] , [83] , [84] , [103] , [105] and with poor differentiation [OR = 2.57 (95% CI = 1.90-3.84, I 2 = 70.4%)] in pooled analysis of 26 studies [17] , [25] , [30] , [33] , [36] , [37] , [39] , [41] , [43] , [44] , [45] , [50] , [52] , [53] , [54] , [58] , [67] , [69] , [72] , [74] , [75] ...…”

Section: Resultsmentioning

confidence: 97%

Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis

Advani

DeSantis

et al. 2018

Translational Oncology

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BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.

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Section: Resultsmentioning

confidence: 97%

Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis

Advani

DeSantis

et al. 2018

Translational Oncology

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“…Additionally, 30 studies reported prevalence of CIMP-low (CIMP-L) and CIMP-0. The pooled prevalence of CIMP-L was 34% (95% CI, 30–39%; I 2 = 94.73%), and the pooled prevalence of CIMP-0 was 47% (95% CI, 40–53%; I 2 = 96.65%) [25, 27, 30, 35, 41, 44–46, 49, 50, 52, 54, 57, 59, 60, 62, 64, 76, 77, 83, 105, 111, 117–119, 121, 123, 126, 131, 133].…”

Section: Resultsmentioning

confidence: 99%

Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer

Advani

Brown

et al. 2019

BMC Cancer

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Background CpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis. Methods We searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques. Results The pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21–24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries. Conclusion Although no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.

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“…Although the clinicopathological significance of EMVI in CRC has already been studied, EMVI based on tumor location and evaluation methods is not available. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Arterial blood is supplied from the outer layer to the inner layer of the gastrointestinal tract and comes out as venous blood. If a tumor cell invades into the vessel, regional, and distant metastases can be induced through the venous flow.…”

Section: Discussionmentioning

confidence: 99%

“…The following data were collected from the full texts of eligible studies: the first author's name, study location, information of tumor, year of publication, number of patients analyzed, evaluation method of venous invasion, the rates of EMVI, and the data for survival rate. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] We did not define a minimal number of patients to be included in a study. The estimated hazard ratio (HR) and its standard error using given parameters, which were the HR point estimate, log-rank statistic or its P value, O-E statistic (difference between numbers of observed and expected events), or its variance, were aggregated.…”

Section: Data Extractionmentioning

confidence: 99%

The Impact of Extramural Venous Invasion in Colorectal Cancer: A Detailed Analysis Based on Tumor Location and Evaluation Methods

2019

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This study aimed to elucidate the prognostic implications of extramural venous invasion (EMVI) in colorectal cancer (CRC) through a meta-analysis. Eighteen eligible studies were included in this meta-analysis. Data on the prevalence of EMVI and the correlation between EMVI and survival were collected from these studies. In addition, a subgroup analysis was conducted based on tumor location and evaluation methods. The estimated prevalence of EMVI was 28.3% (95% confidence interval [CI] = 23.1% to 34.0%) in patients with CRC. The estimated prevalence of EMVI in patients with colon cancer and rectal cancer was 23.0% (95% CI = 17.6% to 29.6%) and 35.7% (95% CI = 22.3% to 51.6%), respectively. Based on the evaluation method, the estimated prevalence of EMVI were 28.3% (95% CI = 23.2% to 34.1%) and 27.3% (95% CI = 8.4% to 60.6%) in pathologic and radiologic examinations, respectively. The correlation of EMVI with worse overall and disease-free survival rates was significant (hazard ratio = 1.773, 95% CI = 1.483-2.120, and hazard ratio = 2.059, 95% CI = 1.683-2.520, respectively). However, in the subgroup analysis with radiologic examination, there was no significant difference in survival rates between patients with and without EMVI. Our study showed that EMVI was frequently detected in 28.3% of patients with CRC and was correlated to worse survival. The detection of EMVI can be useful for predicting the prognosis of patients with CRC.

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DNA hypermethylation as a predictor of extramural vascular invasion (EMVI) in rectal cancer

Cited by 9 publications

References 62 publications

Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis

Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis

Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer

The Impact of Extramural Venous Invasion in Colorectal Cancer: A Detailed Analysis Based on Tumor Location and Evaluation Methods

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