scholarly journals Prognostic value of the combination of microsatellite instability and BRAF mutation in colorectal cancer

2018 ◽  
Vol Volume 10 ◽  
pp. 3911-3929 ◽  
Author(s):  
Yingchi Yang ◽  
Dong Wang ◽  
Lan Jin ◽  
Guocong Wu ◽  
Zhigang Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Value

Overall survival based on MSI and BRAF mutation status for stage II/III colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 132-132
Author(s):  
Sophiya Karki ◽  
Rashna Madan ◽  
Sarah Schmitt ◽  
Ziyan Y. Pessetto ◽  
Andrew K. Godwin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Microsatellite Instability ◽  
Median Survival ◽  
Braf Mutation ◽  
Prognostic Value ◽  
Stage Ii ◽  
Age At Diagnosis ◽  
Mutation Status ◽  
Braf Mutant

132 Background: Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths in the United States. Some of the poor prognostic factors for metastatic CRC (mCRC) include BRAF V600E mutation and microsatellite instability (MSI) that result from mutation or loss of mismatch-repair genes. While the prognostic value of MSI-high CRC for early-stage patients treated with resection and adjuvant chemotherapy is favorable, the prognostic value of BRAF mutation is still unclear. Furthermore, the impact of BRAF mutation with concurrent microsatellite instability on overall survival has not been well investigated. Methods: Here, we collected BRAF mutation status and MSI status of stage II/III CRC patients (n=106) treated at the University of Kansas Cancer Center between September 2009 and July 2020 and compared overall survival between 4 subtypes:MSI-H/BRAF mutant (n=16), MSS/BRAF mutant (n=4), MSI-H/BRAF WT (n=17) and MSS/BRAF WT (n=69), further stratifying patients by age at diagnosis and tumor location. Molecular data were obtained from molecular oncology laboratory as PCR or IHC-based or acquired from outside records. Subgroup analyses were done for stage II and stage III cancers. Results: Table shows the patient characteristics. From our preliminary analysis, MSI-H CRC was found to be primarily a right-sided tumor (MSI-H/BRAF mutant: 94% and MSI-H/BRAF WT 76%). On the contrary, MSS CRC had a more heterogenous localization, spanning left colon, right colon and rectum. In our patient cohort, median survival was not reached for stage II patients whereas for stage III patients, BRAF mutation was associated with poor median survival irrespective of MSI status (MSS/BRAF mutant: 27 months and MSI-H/BRAF mutant 29 months). Median overall survival was found to be 87 months, not reached, 27 months and 29 months for MSS/BRAF WT, MSI-H/BRAF WT, MSS/BRAF mutant and MSI-H/BRAF mutant, respectively. Although associated with poor survival, MSI-H/BRAF mutant displayed later age at diagnosis (mean age 73) compared to MSS/BRAF mutant (mean age 60, p-value<0.029). Conclusions: Our finding suggests that BRAF mutation has poor prognosis even at earlier stages of the disease and that MSS/BRAF mutation, in particular, has the worst prognostic features. These findings highlight the need for BRAF-targeted therapy for CRC at any stage. Due to small sample size, however, our results warrant validation in a larger cohort. [Table: see text]

scholarly journals Prognostic Value of Autophagy, Microsatellite Instability, and KRAS Mutations in Colorectal Cancer

2021 ◽  
Vol 12 (12) ◽  
pp. 3515-3528
Author(s):  
Yuanyuan Wang ◽  
Zhi Zhao ◽  
Jing Zhuang ◽  
Xinxin Wu ◽  
Zhizhong Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Value ◽  
Kras Mutations

scholarly journals Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity within tumor-related genes in colorectal cancer

2019 ◽  
Author(s):  
Xueyun Huo ◽  
Dandan Feng ◽  
Shuangyue Zhang ◽  
Zhenkun Li ◽  
Xiaohong Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Loss Of Heterozygosity ◽  
Clinical Features ◽  
Lymphatic Metastasis ◽  
Predictive Value ◽  
Prognostic Value ◽  
Mucinous Carcinoma ◽  
The Relationship ◽  
Very High

Abstract Background: Microsatellite instability (MSI) has been known as a biomarker for better outcome in colorectal cancer (CRC). However, the conclusion is controversy. In addition, MS can also be a useful marker for loss of heterozygosity (LOH) of genes but it has not been well studied yet. Here, aimed to clarify the predictive value of MSI/LOH within tumor-related genes in CRCs, we detected MSI/LOH of MSs in tumor-related genes and the Bethesda (B5) panel and further analyzed the relationship between MSI/LOH and clinical features or outcomes. Results: As expected, the MSI rate of B5 loci were all very high, suggesting that B5 panel criterion is powerful for MSI status determining of CRCs. Interestingly, MSI/LOH of 2 loci in the B5 panel and 12 loci in tumor-related genes were associated with poorer outcome while MSI/LOH of B5 panel was failed to predict outcomes of CRCs. MSI of BAT25, MSI/LOH of BAT26 and MSI of B5 panel showed closer relationship with mucinous carcinoma. In addition, LOH-H of B5 panel associated with more lymphatic metastasis. Conclusions: In summary, MSI/LOH of certain loci or whole panel of B5 were related to the clinical features, and several loci within tumor-related genes showed a prognostic value in outcomes of CRCs.

Prognostic Value of BRAF and KRAS Mutation in Relation to Colorectal Cancer Survival in Iranian Patients: Correlated to Microsatellite Instability

2019 ◽  
Vol 51 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Ehsan Nazemalhosseini-Mojarad ◽  
Roya Kishani Farahani ◽  
Maryam Mehrizi ◽  
Kaveh Baghaei ◽  
Mohammad Yaghoob Taleghani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Kras Mutation ◽  
Prognostic Value ◽  
Cancer Survival ◽  
Colorectal Cancer Survival ◽  
Iranian Patients

scholarly journals Prognostic value of microsatellite instability in adjuvant treatment of colorectal cancer

2018 ◽  
Vol 72 ◽  
pp. 540-546
Author(s):  
Oleksii A. Potapov ◽  
Anastasia Y. Glagolieva ◽  
Dmytro E. Makhmudov ◽  
Andrzej L. Komorowski
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Adjuvant Treatment ◽  
Prognostic Value ◽  
Treatment Strategies ◽  
Current Status ◽  
Molecular Profile ◽  
Repair System ◽  
Dna Mismatch Repair System ◽  
Analytic Review

The dynamics of morbidity and mortality in colorectal cancer (CRC) has changed little in recent years and consistently remains at a high level. The carcinogenesis of this type of tumors includes a large number of genetic disorders and epigenetic changes, which show a number of features specific for this nosology, providing the basis for the first consensus classification of molecular subtypes for colorectal cancer. One of the main mechanisms chosen as crucial for this classification is the microsatellite instability (MSI) caused by defects in the DNA Mismatch Repair System (MMR). The clinical significance of this CRC molecular profile parameter is hard to overestimate. Over the past three decades, the MSI and MMR have been actively studied for prognosis evaluation, determination of need and selection of appropriate adjuvant chemotherapy scheme for CRC. Despite the significant accumulation of clinical and experimental study data, currently the prognostic value of this parameter is still not well defined with reference to CRC adjuvant treatment strategies, and the released data remain controversial. The purpose of this analytic review is to analyze the current status of MSI and MMR in the setting of adjuvant treatment of CRC patients from a perspective of evidence-based medicine.

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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