scholarly journals Era of universal testing of microsatellite instability in colorectal cancer

2013 ◽  
Vol 5 (2) ◽  
pp. 12 ◽  
Author(s):  
Xuchen Zhang ◽  
Jia Li
2019 ◽  
Vol 8 (4) ◽  
pp. 558 ◽  
Author(s):  
Eriksson ◽  
Amonkar ◽  
Al-Jassar ◽  
Lambert ◽  
Malmenäs ◽  
...  

The study objective was to assess US physicians’ Mismatch Repair/Microsatellite Instability (MMR/MSI) testing practices for metastatic colorectal cancer (mCRC) patients. A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC patients in the US. Eligible physicians were US-based with at least 5 years of experience treating CRC patients, had at least one mCRC patient in their routine care in the past 6 months, and had ordered at least one MMR/MSI test for CRC in the past 6 months. Descriptive and logistic regression analyses were performed. Awareness of specific MMR/MSI testing guidelines was high (n = 127, 84.1%). Of those, 93.7% (119/127) physicians had awareness of specific published guidelines with majority 67.2% (80/119) being aware of National Comprehensive Cancer Network (NCCN) guidelines. Universal testing for all CRC patients was performed by 68.9% (104/151) physicians, while 29.8% (45/151) selectively order the test for some CRC patients. Key barriers for testing included insufficient tissue sample (48.3%, 73/151), patient declined to have the test done (35.8%, 54/151) and insurance cost concerns for patients (31.1%, 47/151), while 27.2% (41/151) reported no barriers. The survey demonstrated high awareness and compliance with MMR/MSI testing guidelines although universal testing rates seem to be suboptimal.


2021 ◽  
Author(s):  
Iiris Ukkola ◽  
Pirjo Nummela ◽  
Annukka Pasanen ◽  
Mia Kero ◽  
Anna Lepistö ◽  
...  

AbstractUniversal testing of microsatellite instability (MSI) is recommended for colorectal cancer (CRC) and endometrial cancer (EC) to screen for Lynch syndrome and to aid in assessing prognosis and optimal treatment. We compared the performance of Idylla MSI test to immunohistochemistry (IHC) of mismatch repair (MMR) proteins in consecutive series of 100 CRC and 108 EC samples, as well as in retrospective series of 28 CRC and 33 EC specimens with known deficient MMR protein expression. The concordance between the Idylla test and IHC was 100% in all CRC samples (n=128) but lower in EC samples (87.2%; n=141). In the EC samples, sensitivity of Idylla test was 72.7% and specificity 100%. EC MSI/dMMR agreement was 85.4% for MLH1, 87.5% for MSH2, and only 35.3% for MSH6. When we analyzed 14 EC samples that were discrepant, i.e., dMMR using IHC and microsatellite stable using Idylla, with microsatellite markers BAT25 and BAT26, we found four cases to be replication error (RER) positive. All RER positive cases were deficient for MSH6 protein expression. We also re-analyzed EC samples with variable tumor cellularity to determine the limit of detection of the Idylla test and found that a 30% or higher tumor cellularity is required. We conclude that Idylla MSI test offers a sensitive and specific method for CRC diagnostics but is less sensitive in EC samples especially in the case of MSH6 deficiency.


2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  

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


1998 ◽  
Vol 22 (5) ◽  
pp. 383-395 ◽  
Author(s):  
Pilar Iniesta ◽  
Carmen de Juan ◽  
Trinidad Caldes ◽  
Francisco-Jose Vega ◽  
Maria-Jose Massa ◽  
...  

2010 ◽  
Vol 16 (6) ◽  
pp. 1845-1855 ◽  
Author(s):  
Anna M. Dahlin ◽  
Richard Palmqvist ◽  
Maria L. Henriksson ◽  
Maria Jacobsson ◽  
Vincy Eklöf ◽  
...  

2021 ◽  
pp. 1-9
Author(s):  
Wen Wang ◽  
Guangyu Wang ◽  
Shuang Fu ◽  
Beibei Zhang ◽  
Zengyao Liu ◽  
...  

BACKGROUND: Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis and a more effective immune response than patients with microsatellite stable (MSS) CRC. Moreover, activated platelets play a crucial role in modulating innate immune cells. Mean platelet volume (MPV) is an indicator of platelet activation. This study is to examine the association between MPV and MSI status in CRC. METHODS: We collected the clinical and pathological variables of 424 CRC patients diagnosed at the Harbin Medical University Cancer Hospital from January 2018 to December 2018. Associations between MPV levels and MSI status were examined. Propensity score matching (PSM) was performed to reduce the possibility of selection bias. RESULTS: 424 CRC patients were divided into low-MPV group and high-MPV group according to the optimal cut-off value of MPV. 131 high-MPV patients were matched to low-MPV counterparts in a 1:1 ratio by propensity score matching. As MPV levels increased, the percentage of patients with MSI-H reduced. Furthermore, compared with MSS group, the MSI-H group had a significantly lower MPV levels (p= 0.003 after matching). In addition, logistic regression analysis identified reduced MPV as an independent risk factor for MSI-H in CRC patients after controlling for other potential parameters. CONCLUSION: Lower MPV is associated with MSI-H subtype of CRC. Further study on MPV in MSI-H CRC is warranted.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Neemat M. Kassem ◽  
Gamal Emera ◽  
Hebatallah A. Kassem ◽  
Nashwa Medhat ◽  
Basant Nagdy ◽  
...  

Abstract Background Colorectal cancer (CRC) is the third most common cause of cancer-related deaths which contributes to a significant public health problem worldwide with 1.8 million new cases and almost 861,000 deaths in 2018 according to the World Health Organization. It exhibits 7.4% of all diagnosed cancer cases in the region of the Middle East and North Africa. Molecular changes that happen in CRCs are chromosomal instability, microsatellite instability (MSI), and CpG island methylator phenotype. The human RAS family (KRAS, NRAS, and HRAS) is the most frequently mutated oncogenes in human cancer appearing in 45% of colon cancers. Determining MSI status across CRCs offers the opportunity to identify patients who are likely to respond to targeted therapies such as anti-PD-1. Therefore, a method to efficiently determine MSI status for every cancer patient is needed. Results KRAS mutations were detected in 31.6% of CRC patients, namely in older patients (p = 0.003). Codons 12 and 13 constituted 5/6 (83.3%) and 1/6 (16.7%) of all KRAS mutations, respectively. We found three mutations G12D, G12C, and G13D which occur as a result of substitution at c.35G>A, c.34G>T, and c.38G>A and have been detected in 4/6 (66.6%), 1/6 (16.7%), and 1/6 (16.7%) patients, respectively. Eleven (57.9%) patients had microsatellite instability-high (MSI-H) CRC. A higher percentage of MSI-H CRC was detected in female patients (p = 0.048). Eight patients had both MSI-H CRC and wild KRAS mutation with no statistical significance was found between MSI status and KRAS mutation in these studied patients. Conclusion In conclusion, considering that KRAS mutations confer resistance to EGFR inhibitors, patients who have CRC with KRAS mutation could receive more tailored management by defining MSI status. MSI-high patients have enhanced responsiveness to anti-PD-1 therapies. Thus, the question arises as to whether it is worth investigating this association in the routine clinical setting or not. Further studies with a larger number of patients are needed to assess the impact of MSI status on Egyptian CRC care.


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