scholarly journals Microsatellite Instability in Colorectal Cancer Liquid Biopsy—Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 544
Author(s):  
Francis Yew Fu Tieng ◽  
Nadiah Abu ◽  
Learn-Han Lee ◽  
Nurul-Syakima Ab Mutalib
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Liquid Biopsy ◽  
Predictive Marker ◽  
High Concentration ◽  
Inherited Cancer ◽  
Normal Tissues ◽  
Non Invasive ◽  
Highly Sensitive ◽  
Interesting Possibility

Colorectal cancer (CRC) is the third most commonly-diagnosed cancer in the world and ranked second for cancer-related mortality in humans. Microsatellite instability (MSI) is an indicator for Lynch syndrome (LS), an inherited cancer predisposition, and a prognostic marker which predicts the response to immunotherapy. A recent trend in immunotherapy has transformed cancer treatment to provide medical alternatives that have not existed before. It is believed that MSI-high (MSI-H) CRC patients would benefit from immunotherapy due to their increased immune infiltration and higher neo-antigenic loads. MSI testing such as immunohistochemistry (IHC) and PCR MSI assay has historically been a tissue-based procedure that involves the testing of adequate tissue with a high concentration of cancer cells, in addition to the requirement for paired normal tissues. The invasive nature and specific prerequisite of such tests might hinder its application when surgery is not an option or when the tissues are insufficient. The application of next-generation sequencing, which is highly sensitive, in combination with liquid biopsy, therefore, presents an interesting possibility worth exploring. This review aimed to discuss the current body of evidence supporting the potential of liquid biopsy as a tool for MSI testing in CRC.

Microsatellite instability: a predictive marker in metastatic colorectal cancer?

2009 ◽  
Vol 4 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Gaëtan Des Guetz ◽  
Bernard Uzzan ◽  
Patrick Nicolas ◽  
Olivier Schischmanoff ◽  
Jean-François Morere
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Predictive Marker

scholarly journals Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4500
Author(s):  
Isabel Heidrich ◽  
Thaer S. A. Abdalla ◽  
Matthias Reeh ◽  
Klaus Pantel
Keyword(s):  
Colorectal Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Personalized Therapy ◽  
Liquid Biopsies ◽  
Curative Surgery ◽  
Non Invasive ◽  
Staging Systems

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. It is a heterogeneous tumor with a wide genomic instability, leading to tumor recurrence, distant metastasis, and therapy resistance. Therefore, adjunct non-invasive tools are urgently needed to help the current classical staging systems for more accurate prognostication and guiding personalized therapy. In recent decades, there has been an increasing interest in the diagnostic, prognostic, and predictive value of circulating cancer-derived material in CRC. Liquid biopsies provide direct non-invasive access to tumor material, which is shed into the circulation; this enables the analysis of circulating tumor cells (CTC) and genomic components such as circulating free DNA (cfDNA), which could provide the key for personalized therapy. Liquid biopsy (LB) allows for the identification of patients with a high risk for disease progression after curative surgery, as well as longitudinal monitoring for disease progression and therapy response. Here, we will review the most recent studies on CRC, demonstrating the clinical potential and utility of CTCs and ctDNA. We will discuss some of the advantages and limitations of LBs and the future perspectives in the field of CRC management.

Detection of microsatellite instability (MSI) in colorectal cancer samples with a novel set of highly sensitive markers by means of the Idylla MSI Test prototype.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e15639-e15639 ◽  
Author(s):  
Bram De Craene ◽  
Jan Van de Velde ◽  
Evelien Rondelez ◽  
Liesbeth Vandenbroeck ◽  
Kelly Peeters ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Highly Sensitive

scholarly journals A Comprehensive Study of Microsatellite Instability Testing And Its Comparison With Immunohistochemistry In Gastric And Colorectal Cancers

2021 ◽  
Author(s):  
Yujun Park ◽  
Soo Kyung Nam ◽  
Soo Hyun Seo ◽  
Kyoung Un Park ◽  
Sang-Hoon Ahn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Expression Patterns ◽  
Routine Clinical Practice ◽  
Colorectal Cancers ◽  
Normal Tissues ◽  
Low Incidence ◽  
Mmr Proteins ◽  
Comprehensive Study

Abstract Background Microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for the mismatch repair (MMR) protein in gastric cancer (GC) and colorectal cancer (CRC). Methods PCR-based MSI testing was performed to compare the tumor and non-neoplastic normal tissues using five microsatellites consisting of two mononucleotide (BAT-26, BAT-25) and three dinucleotide (D5S346, D2S123, and D17S250) in 5,676 GC and 2,553 CRC cases. IHC for the MMR protein MLH1 was done in GCs, and IHC for four MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed in CRCs. Reviews were carried out for discordant or indeterminate IHC cases (such as focal loss of expression, equivocal expression, or abnormal expression patterns). Results MSI-high (MSI-H) and MMR-deficient (dMMR) expression was observed in 521 (9.2%) GC and 171 (6.7%) CRC cases. Discordance between MSI testing and IHC as well as indeterminate IHC cases accounted for 54 (0.9%) and 29 (1.1%) cases out of all GC and CRC cases, respectively, but accounted for 9.4% and 14.1% out of 575 GC and 205 CRC cases, respectively, excluding unequivocal microsatellite stable/MSI-low and MMR-proficient (pMMR) expression cases. pMMR expression was observed in most of the MSI-H GCs and CRCs consisting of only one unstable BAT-25 mononucleotide marker or solely of dinucleotide markers. ConclusionsConsidering the low incidence of MSI-H or dMMR expression, discordant or indeterminate IHC and/or MSI results were occasionally identified in GC and CRC cases, requiring complementary testing. These findings provide evidence for MSI testing and MMR IHC in routine clinical practice.

scholarly journals Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression

2020 ◽  
Vol 21 (12) ◽  
pp. 4494
Author(s):  
Ana Florencia Vega-Benedetti ◽  
Eleonora Loi ◽  
Loredana Moi ◽  
Sandra Orrù ◽  
Pina Ziranu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cell Signalling ◽  
Cpg Islands ◽  
Digital Pcr ◽  
Protein Levels ◽  
Normal Tissues ◽  
Non Invasive ◽  
Cancer Early Detection ◽  
Stool Samples

Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC.

Fecal microRNAs as non-invasive biomarkers for the detection of colorectal cancer: a systematic review

2019 ◽  
Vol 31 (1) ◽  
Author(s):  
Antonio Francavilla ◽  
Sonia Tarallo ◽  
Barbara Pardini ◽  
Alessio Naccarati
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Non Invasive

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

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