Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location

Jm, Bae; Kim, Jae-Hoon; Ny, Cho; Ty, Kim; Kang, Gyeong Hoon

doi:10.1038/bjc.2013.430

Cited by 102 publications

(85 citation statements)

References 58 publications

(76 reference statements)

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“…When subgroup analysis was performed, CIMP was found to be an indicator of poor prognosis only in MSS, and not in MSI tumors (comparable to BRAF mutation status). These data are well in the line with an earlier study by Bae et al [72], who noted prognostic implications of CIMP status only in distal tumors.…”

Section: Microsatellite Instability In Sporadic Colorectal Cancersupporting

confidence: 93%

Microsatellite instability in colorectal cancer: clinicopathological significance

Setaffy¹,

Langner²

2015

pjp

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Although often viewed as a single disease, colorectal cancer more accurately represents a constellation of heterogeneous subtypes that result from different combinations of genetic events and epigenetic alterations. Chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) have been identified as the three major molecular characteristics, which interact with other significant mutations, such as mutations in the KRAS and BRAF genes. High-level MSI (MSI-H) is of eminent clinical importance. It is the seminal molecular feature for the identification of individuals with Lynch syndrome, but it may also occur in sporadic cancers with CIMP phenotype, which arise from serrated precursor lesions. MSI-H status is a marker of favorable prognosis and may be used for outcome prediction, that is, molecular grading. Among others, mucinous and medullary histology, signet-ring cell differentiation, and a marked anti-tumoral immune response are histological features suggesting MSI. Universal tumor testing is recommended and may be performed using immunohistochemistry (mismatch repair protein expression) or molecular analysis, as has recently been recommended by an international task force. In this review, we consider in detail the molecular pathogenesis of colorectal cancer, focusing on the diagnosis of MSI in both hereditary and sporadic tumors.

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Section: Microsatellite Instability In Sporadic Colorectal Cancersupporting

confidence: 93%

Microsatellite instability in colorectal cancer: clinicopathological significance

Setaffy¹,

Langner²

2015

pjp

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“…This has been shown in patient studies, where CIMP-H was shown to associate with older female patients, smoking, proximal location, MSI-H tumours and BRAF mutations [10]. This study also noted a proximal location of CIMP-H tumours, and this has been reported in other studies where it was suggested that CIMP-H and MSI-H increase from the rectum to the caecum [26]. This is interesting as it is thought there is a similar distribution of local inflammation across CRC tumours, and CIMP-H/MSI-H/BRAF mutant tumours are also associated with an increase in intra-tumour inflammation characterised by a lymphocytic infiltration [8].…”

Section: Cms1: Msi Immunesupporting

confidence: 85%

Colorectal cancer subtypes: Translation to routine clinical pathology

Roseweir

McMillan

Horgan

et al. 2017

Cancer Treatment Reviews

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Colorectal cancer (CRC) is the second most common cause of cancer death in Europe.Although outcomes have improved, it is clear that from a genomic standpoint CRC is not one disease, but a heterogeneous group of malignancies that arise within one organ. Given that different subtypes have different outcomes, the ability to subtype tumours in the clinic would be highly favourable, enabling optimal treatment for individual patients.In 2015, a consortium proposed four consensus subtypes for CRC (MSI immune, canonical, metabolic, and mesenchymal) based on six classifications systems reported to have prognostic value.However, genomic assessment of tumours is not readily translated into routine pathology with a need for standardisation and reproducibility of assessment. Immunohistochemistry is widely used in routine pathology, and would present a more readily translatable method for subtyping CRC tumours. Therefore, the literature was reviewed to characterise the genomic and phenotypic features associated with each subtype, with the aim of enabling subtyping of CRC to be taken forward into routine clinical practice.

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“…This study demonstrated that the frequencies of CIMP-high, MSI-high, and BRAF and PIK3CA mutations in colorectal cancer increase gradually from rectum to ascending colon, challenging the notion of an acute transition at the splenic flexure (131). Independent studies have confirmed similar distributions in molecular features of colorectal cancers (34, 161–163). Furthermore, in synchronous colorectal cancers, molecular similarities are proportional to the physical proximity of the two cancers (164).…”

Section: Colorectal Continuummentioning

confidence: 74%

Progress and Opportunities in Molecular Pathological Epidemiology of Colorectal Premalignant Lesions

Lochhead

Chan

Giovannucci

et al. 2014

American Journal of Gastroenterology

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Molecular pathological epidemiology (MPE) is integrative molecular and population health science to address molecular pathogenesis and heterogeneity of disease processes. MPE of colon and rectal premalignant lesions (including hyperplastic polyps, tubular adenomas, tubulovillous adenomas, villous adenomas, traditional serrated adenomas, sessile serrated adenomas / sessile serrated polyps, and hamartomatous polyps) can provide unique opportunities to examine the influence of diet, lifestyle and environmental exposures on specific pathways of carcinogenesis. Colorectal neoplasia can provide a practical model where both malignant epithelial tumor (carcinoma), and its precursor, are subjected to molecular pathology analyses. KRAS, BRAF, and PIK3CA oncogene mutations, microsatellite instability, CpG island methylator phenotype, and LINE-1 methylation are commonly-examined tumor biomarkers. Future opportunities include comprehensive interrogation of genomics, epigenomics and pan-omics, as well as in vivo pathology analyses of tissue microenvironment, molecular networks and interactome by endomicroscopy. Considering the colorectal continuum hypothesis and emerging roles of gut microbiota and host immunity in tumorigenesis, detailed tumor location is important information. There are unique strengths and caveats, especially with regard to case ascertainment by colonoscopy. MPE of colorectal premalignant lesions can identify etiologic exposures associated with neoplastic initiation and progression, help us better understand colorectal carcinogenesis, and facilitate personalized prevention, screening, and therapy.

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Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location

Cited by 102 publications

References 58 publications

Microsatellite instability in colorectal cancer: clinicopathological significance

Microsatellite instability in colorectal cancer: clinicopathological significance

Colorectal cancer subtypes: Translation to routine clinical pathology

Progress and Opportunities in Molecular Pathological Epidemiology of Colorectal Premalignant Lesions

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