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Microsatellite Instability

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The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.

Also Known As:

Replication Error Phenotype; Error Phenotype, Replication; Error Phenotypes, Replication; Instability, Microsatellite; Phenotype, Replication Error; Phenotypes, Replication Error; Replication Error Phenotypes

Networked: 3512 relevant articles (40 outcomes, 331 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Colorectal Neoplasms (Colorectal Cancer)
2.	Neoplasms (Cancer)
3.	Colonic Neoplasms (Colon Cancer)
4.	Hereditary Nonpolyposis Colorectal Neoplasms (Hereditary Nonpolyposis Colorectal Cancer)
5.	Carcinoma (Carcinomatosis)

Experts

1.	Ogino, Shuji: 68 articles (09/2015 - 01/2006)
2.	Fuchs, Charles S: 64 articles (09/2015 - 01/2006)
3.	Nosho, Katsuhiko: 47 articles (09/2015 - 05/2005)
4.	Thibodeau, Stephen N: 43 articles (10/2015 - 02/2002)
5.	Boland, C Richard: 37 articles (06/2015 - 07/2002)
6.	Goel, Ajay: 37 articles (05/2015 - 01/2003)
7.	Shima, Kaori: 34 articles (07/2013 - 01/2008)
8.	Lee, Sug Hyung: 30 articles (11/2015 - 12/2006)
9.	Yoo, Nam Jin: 30 articles (11/2015 - 12/2006)
10.	Baba, Yoshifumi: 30 articles (09/2015 - 01/2009)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Microsatellite Instability:

1.	N-methylsuccinimideIBA 01/01/2013 - "Microsatellite instability (MSI) is associated with improved node harvest, but the association to other genetic factors is largely unknown. " 10/01/2014 - "The aim of the present study was to determine the frequency of KRAS and BRAF mutations and microsatellite instability (MSI) in CRC precursor lesions, to evaluate the association between molecular, pathologic and morphologic alterations in precursor lesions and to compare with the alterations detected in CRC. " 01/01/2014 - "The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions. " 12/01/2013 - "Immunohistochemical (IHC) analysis and microsatellite instability (MSI) studies, genetic testing, a literature and online MMR mutation database review, in silico phenotype prediction tools, and an in vitro MMR activity assay were used to study the clinical significance of this variant. " 10/01/2013 - "The median sample size of studies was 112, 74% were retrospective case-series and 70% performed microsatellite instability (MSI) analysis to evaluate the status of MMR. "
2.	Fluorouracil (Carac)FDA LinkGeneric 02/01/2004 - "In vitro studies suggest that microsatellite instability influences cell survival after 5-fluorouracil treatment. " 01/05/2012 - "Epigenetic alterations of TFAP2E were independent of mutations in key regulatory cancer genes, microsatellite instability, and other genes that affect fluorouracil metabolism. " 12/03/2011 - "Microsatellite instability, a well known prognostic factor, might be predictive for a lack of activity of fluorouracil treatment in some stage II patients. " 02/01/2010 - "Moreover, the detection of mismatch-repair deficiency or high-degree microsatellite instability indicates unresponsiveness to 5-FU monotherapy. " 02/01/2004 - "However, the benefit of 5-fluorouracil was different between microsatellite instability-high and non-microsatellite instability-high groups. "
3.	DNA (Deoxyribonucleic Acid)IBA 10/01/2006 - "In this study, we examined 19 cases of LEC from the United States for evidence of microsatellite instability at the DNA level and for alterations in the DNA mismatch repair (MMR) system at the immunohistochemical staining level. " 09/01/1999 - "Since reference DNA was extracted from corresponding fresh samples of non-cancerous liver tissue, the incidence of microsatellite instability in non-cancerous liver tissues was not assessed in this study. " 01/01/1999 - "Three cases had insufficient DNA for microsatellite instability studies. " 08/01/2015 - "TP53 mutation, allelic deletion of the APC gene and nuclear staining of β-catenin are frequently detected in the intestinal phenotype of GC, whereas CDH1 gene mutation, microsatellite instability and DNA hypermethylation of MLH1 are common events in the gastric phenotype of GC. " 08/01/2015 - "Genetic alterations detected in CA-CRC such as genetic mutations, microsatellite instability, and DNA hypermethylation are also recognized in sporadic CRC; however, there are differences in the timing and frequency of molecular events between CA-CRC and sporadic CRC. "
4.	Calcibiotic Root Canal SealerIBA 01/01/2015 - "To clarify its role in colorectal carcinogenesis, mitochondrial microsatellite instability (mtMSI) and other markers were investigated in CRCs and their precancerous lesions, as a multitier genetic study. " 07/10/2013 - "All incident CRCs were analyzed for mismatch repair protein loss, supported by BRAF mutation and microsatellite instability testing. " 05/01/2013 - "CIMP-positive CRCs are associated with a proximal location in the colon, microsatellite instability, BRAF mutation and a relatively poor clinical outcome. " 07/01/2010 - "Four of the 5 CRCs demonstrated a high microsatellite instability phenotype. " 01/01/2009 - "We present 2 nearly equivalent logistic regression models for clinical use that predict microsatellite instability based on the review of 1649 CRCs from patients of all ages collected in a population-based case control study in northern Israel. "
5.	Thymidylate SynthaseIBA 01/01/2006 - "The objective of the present investigation was to determine whether microsatellite instability is associated with thymidylate synthase expression. " 11/01/2007 - "Colorectal carcinomas with microsatellite instability display increased thymidylate synthase gene expression levels." 05/01/2006 - "Thymidylate synthase expression in colon carcinomas with microsatellite instability." 01/01/2006 - "Inter-relationship between microsatellite instability, thymidylate synthase expression, and p53 status in colorectal cancer: implications for chemoresistance." 06/01/2005 - "High thymidylate synthase expression in colorectal cancer with microsatellite instability: implications for chemotherapeutic strategies."
6.	irinotecan (Camptosar)FDA LinkGeneric 11/18/2008 - "Microsatellite instability due to hMLH1 deficiency is associated with increased cytotoxicity to irinotecan in human colorectal cancer cell lines." 02/01/2000 - "Sensitivity to CPT-11 of xenografted human colorectal cancers as a function of microsatellite instability and p53 status." 09/15/2003 - "Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer." 10/01/2000 - "Our preliminary data suggest that intragenic microsatellite instability may influence tumor response to CPT-11 in patients with colorectal cancer." 09/01/2004 - "We conclude that a molecular profile characterized by high microsatellite instability with loss of mismatch repair protein expression and p21WAF1/C1PI is predictive of an improved response to neoadjuvant treatment with 5-FU, CPT-11 and radiation therapy."
7.	Leucovorin (Folinic Acid)FDA Link 10/20/2002 - "High-frequency microsatellite instability predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative bowel resection." 03/01/2003 - "The aim of this work was to investigate the relationship between microsatellite instability (MSI), treatment response and survival in palliative patients with colorectal cancer (CRC) undergoing first-line treatment with weekly 24-hour infusion (24-h inf.) of high-dose 5-fluorouracil (5-FU) and folinic acid (FA). " 04/01/2010 - "Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin." 04/10/2009 - "Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803." 05/01/2013 - "The prognostic impact of CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the treatment outcome of colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) is unclear. "
8.	Proteins (Proteins, Gene)IBA 10/01/1999 - "Western blot analysis of DNA mismatch repair proteins revealed a marked decrease of expression of PMS2 in U2-OS/Pt cells, which also exhibited microsatellite instability. " 03/01/2012 - "The purpose of this study was to investigate the expression of DNA repair proteins, and the possible occurrence of microsatellite instability in HT1. " 02/01/2007 - "MLH1 and MSH2 were studied by direct sequencing in all the 99 patients, and the study of microsatellite instability and of MMR proteins expression was performed. " 05/05/2005 - "Among patients whose screening results were positive for microsatellite instability, we searched for germ-line mutations in the MLH1, MSH2, MSH6, and PMS2 genes with the use of immunohistochemical staining for mismatch-repair proteins, genomic sequencing, and deletion studies. " 10/01/2015 - "Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. "
9.	Aspirin (Acetylsalicylic Acid)FDA LinkGeneric 01/01/1999 - "[Aspirin suppresses microsatellite instability]." 01/01/2003 - "It was demonstrated recently that aspirin results in reduced microsatellite instability in colorectal cancer cells. " 11/15/2007 - "Nitric oxide-donating aspirin derivatives suppress microsatellite instability in mismatch repair-deficient and hereditary nonpolyposis colorectal cancer cells." 11/15/2007 - "Aspirin and sulindac have been shown to be effective in selecting for cells with reduced microsatellite instability (MSI) that is inherent in mismatch repair (MMR)-deficient hereditary nonpolyposis colorectal cancer (HNPCC) cells. " 01/01/1999 - "Six colorectal cancer cell lines all but one deficient for human mismatch repair (MMR) genes were examined for microsatellite instability (MSI) prior and after treatment with Aspirin or Sulindac. "
10.	AntigensIBA 03/01/2013 - "In CRC with microsatellite instability, several immunogenic neo-antigens have been identified and could explain the high level of tumor infiltrating lymphocytes and the better prognosis of this type of tumour. " 08/01/2004 - "[Microsatellite instability and loss of heterozygosity of human leucocyte antigen class I gene in cervical carcinoma]." 01/01/2011 - "We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. " 01/01/2009 - "It has been suggested that high levels of T regs are detrimental to the patient in some forms of cancer, but the role of these antigen-specific cells in individuals with colorectal cancers with high levels of microsatellite instability is unknown. " 05/15/2005 - "Frequent immune responses to a cancer/testis antigen, CAGE, in patients with microsatellite instability-positive endometrial cancer."

Therapies and Procedures

1.	Adjuvant Chemotherapy 01/01/2015 - "Furthermore, patients exhibiting microsatellite stability or low-frequency instability who received adjuvant chemotherapy had a better 5-year rate of DFS than patients did not (HR, 5.16 [95% CI, 2.90 to 9.18]; p< 0.001), while patients exhibiting high-frequency microsatellite instability were not connected with increased DFS (p= 0.696). " 01/01/2011 - "The presence of microsatellite instability and CpG island methylator phenotype (CIMP) were assessed and 131 microsatellite stable/CIMP- cases were selected for survival analysis, of which 77 patients had received postoperative adjuvant chemotherapy with oral fluoropyrimidines. " 07/17/2003 - "By contrast, there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability. " 07/17/2003 - "Among patients who received adjuvant chemotherapy, high-frequency microsatellite instability was not correlated with increased overall survival (hazard ratio for death, 1.07 [95 percent confidence interval, 0.62 to 1.86]; P=0.80). " 12/01/2009 - "The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm, or microsatellite instability status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. "
2.	Drug Therapy (Chemotherapy) 04/02/2005 - "In this study, associations between high degree of microsatellite instability and pathological (location, mucinous content, differentiation grade, stages T3N0, stages II and III) and clinical features (response to chemotherapy, disease-free survival and overall survival) were evaluated. " 02/01/2015 - "A few of these markers, such as microsatellite instability and the CpG island methylator phenotype (CIMP), show promise as predictive markers for cytotoxic chemotherapy. " 01/01/2015 - "The 92 patients (21%) with BRAF mutation had a poor prognosis regardless of microsatellite instability, but receipt of 1-2nd chemotherapy was similar to wildtype BRAF patients. " 08/01/2013 - "One patient with mutated DPD was not treated with chemotherapy upon the clinician's decision because of his DPD mutated genotype and the presence of microsatellite instability. " 03/01/2011 - "• The biology underlying chemotherapy resistance in late relapse could be related to a high incidence of microsatellite instability and BRAF mutation V600E, which were found in half of the patients."
3.	Transplantation (Transplant Recipients) 05/01/2014 - "To study the inhibitory effect of Xiaotan Sanjie Recipe (XSR) on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice. " 05/01/2014 - "[Inhibitory effect of Xiaotan Sanjie Recipe on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice]." 12/01/2004 - "The clinical research advances included the efficacy of infliximab in the treatment of fistulizing Crohn's disease, survival after isolated intestinal transplantation, the role of endoscopic treatment of bleeding peptic ulcers and Barrett's esophagus, the recurrence of cancer after laparoscopic colectomy, the impact of microsatellite instability on the response to adjuvant chemotherapy with 5-fluorouracil (5-FU), the epidemiology of obesity and its response to low-carbohydrate diets, the potential role of gastrointestinal factors in the development of obesity, and, the newly appreciated condition, autoimmune pancreatitis with associated cholangitis. "
4.	Colectomy 01/01/2014 - "Metachronous serrated neoplasia is uncommon after right colectomy in patients with methylator colon cancers with a high degree of microsatellite instability." 06/01/1999 - "Sites of cancer, dysplasia, and nondysplasia from 14 UC colectomy cases containing cancer were analyzed for chromosomal alterations by comparative genomic hybridization (CGH) and for microsatellite instability using a series of 10 microsatellite markers. " 09/01/2004 - "A subtotal colectomy was performed and the subsequent microsatellite instability (MSI) analysis revealed high MSI in the resected tumor tissue. " 07/20/2000 - "To search for a genetic basis for this predisposition, we studied the incidence of microsatellite instability (MSI) in paraffin-embedded colectomy specimens of 124 young (<50 years old) Chinese colorectal cancer patients referred to the Hong Kong Hereditary Gastrointestinal Cancer Registry from 1995 to 1998. " 12/01/2004 - "The clinical research advances included the efficacy of infliximab in the treatment of fistulizing Crohn's disease, survival after isolated intestinal transplantation, the role of endoscopic treatment of bleeding peptic ulcers and Barrett's esophagus, the recurrence of cancer after laparoscopic colectomy, the impact of microsatellite instability on the response to adjuvant chemotherapy with 5-fluorouracil (5-FU), the epidemiology of obesity and its response to low-carbohydrate diets, the potential role of gastrointestinal factors in the development of obesity, and, the newly appreciated condition, autoimmune pancreatitis with associated cholangitis. "
5.	Neoadjuvant Therapy 12/01/2000 - "Loss of heterozygosity and microsatellite instability as predictive markers for neoadjuvant treatment in gastric carcinoma." 09/01/2011 - "To address this, rectal adenocarcinomas both before and after neoadjuvant treatment were evaluated for alterations in KRAS and microsatellite instability (MSI) testing. " 09/01/2004 - "We conclude that a molecular profile characterized by high microsatellite instability with loss of mismatch repair protein expression and p21WAF1/C1PI is predictive of an improved response to neoadjuvant treatment with 5-FU, CPT-11 and radiation therapy."