The impact of CpG island methylator phenotype and microsatellite instability on tumour budding in colorectal cancer

Zlobec, Inti; Bihl, Michel; Foerster, Anja; Rufle, Alex; Lugli, Alessandro

doi:10.1111/j.1365-2559.2012.04273.x

Cited by 34 publications

(36 citation statements)

References 33 publications

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“…180, 181 Smoking has also been shown to be a strong risk factor for synchronous primary colorectal cancers (R Nishihara et al, unpublished data) and synchronous multiple polyps, 182 especially serrated polyps, 183 which are recognized as precursors for colorectal cancers with CpG island methylator phenotype, microsatellite instability and/or BRAF mutation. 159, 184–186 CpG island methylator phenotype-high, microsatellite instability-high and BRAF mutation can co-occur in colorectal cancer, 9, 30, 113, 184, 187–195 and are common characteristics of synchronous colorectal cancers. 67–70 Furthermore, synchronous primary colorectal cancers are considered to arise due to some form of predisposition, likely involving both genetic and environmental factors.…”

Section: The Genesis Of the “Etiologic Field Effect”mentioning

confidence: 99%

Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression

et al. 2015

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The term “field effect” (also known as field defect, field cancerization, or field carcinogenesis) has been used to describe a field of cellular and molecular alteration, which predisposes to the development of neoplasms within that territory. We explore an expanded, integrative concept, “etiologic field effect”, which asserts that various etiologic factors (the exposome including dietary, lifestyle, environmental, microbial, hormonal, and genetic factors) and their interactions (the interactome) contribute to a tissue microenvironmental milieu that constitutes a “field of susceptibility” to neoplasia initiation, evolution, and progression. Importantly, etiological fields predate the acquisition of molecular aberrations commonly considered to indicate presence of filed effect. Inspired by molecular pathological epidemiology (MPE) research, which examines the influence of etiologic factors on cellular and molecular alterations during disease course, an etiologically-focused approach to field effect can: 1) broaden the horizons of our inquiry into cancer susceptibility and progression at molecular, cellular, and environmental levels, during all stages of tumor evolution; 2) embrace host-environment-tumor interactions (including gene-environment interactions) occurring in the tumor microenvironment; and, 3) help explain intriguing observations, such as shared molecular features between bilateral primary breast carcinomas, and between synchronous colorectal cancers, where similar molecular changes are absent from intervening normal colon. MPE research has identified a number of endogenous and environmental exposures which can influence not only molecular signatures in the genome, epigenome, transcriptome, proteome, metabolome and interactome, but also host immunity and tumor behavior. We anticipate that future technological advances will allow the development of in vivo biosensors capable of detecting and quantifying “etiologic field effect” as abnormal network pathology patterns of cellular and microenvironmental responses to endogenous and exogenous exposures. Through an “etiologic field effect” paradigm, and holistic systems pathology (systems biology) approaches to cancer biology, we can improve personalized prevention and treatment strategies for precision medicine.

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Section: The Genesis Of the “Etiologic Field Effect”mentioning

confidence: 99%

Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression

et al. 2015

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“…However, the tumors also display distinct features at the histological level, which should raise the suspicion of MSI and prompt further analysis. The following features are commonly seen: mucinous histology, signet-ring cell differentiation, medullary carcinoma, poor differentiation, host response characterized by intra-and peritumoral lymphocytes as well as "Crohn-like" reaction, tumor heterogeneity, lack of "dirty" necrosis, and a "pushing" tumor margin with no or low-level tumor budding (Table V) [73,74,75,76,77,78]. We believe it is worth looking at some of these features in greater detail.…”

Section: Histology Of High-level Microsatellite Instability Colorectamentioning

confidence: 99%

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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“…12 In the context of molecular pathology features, tumor budding is most frequently seen in B-Raf protooncogene, serine/threonine kinase (BRAF)-mutated CRC and is commonly absent in microsatellite instable CRC. 14 Tumor budding has been shown to be inversely correlated to CD81 T-cell infiltration, suggesting a possible T-cell based defense against infiltrating tumor-budding cells in the tumor microenvironment of CRC. 15 However, little is known on how tumor buds evade the immune response during invasion and if oncogenic driver mutations may contribute to this process.…”

Section: Introductionmentioning

confidence: 99%

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome

Koelzer

Dawson

Andersson

et al. 2015

Translational Research

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The impact of CpG island methylator phenotype and microsatellite instability on tumour budding in colorectal cancer

Cited by 34 publications

References 33 publications

Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression

Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression

Microsatellite instability in colorectal cancer: clinicopathological significance

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome

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