scholarly journals Endometrial cancer and microsatellite instability status

Open Medicine ◽  
2014 ◽  
Vol 10 (1) ◽  
Author(s):  
Daiva Kanopiene ◽  
Jolanta Vidugiriene ◽  
Konstantinas Povilas Valuckas ◽  
Giedre Smailyte ◽  
Saule Uleckiene ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Microsatellite Instability ◽  
Myometrial Invasion ◽  
Repair System ◽  
High Status ◽  
Clinicopathologic Characteristics ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Clinicopathologic Parameters ◽  
Analysis System

AbstractMicrosatellite instability (MSI) is an important factor in the development of various cancers as an identifier of a defective DNA mismatch repair system. The objective of our study was to define the association between microsatellite instability status and traditional clinicopathologic characteristics of endometrioid type adenocarcinoma. Material and methods: MSI status of endometrial cancer was examined by employing the Promega MSI Analysis System. This system uses 5 mononucleotide markers to identify MSI in tumour and normal tissue DNA (BAT-25, BAT-26, NR-21, NR-24, and MONO-27), and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. In this study, we investigated MSI status in 109 endometrial carcinomas. Results and conclusions: One hundred (92%) of 109 endometrial cancers showed endometrioid type histology and only 9 (8%) non-endometrioid type. MSI-high was found in 17% (17/100) of endometrioid type adenocarcinomas, in 0% (0/9) of non-endometrioid carcinomas. Selected clinicopathologic parameters for endometrioid type adenocarcinomas were compared to the MSI status which was separated into two groups – MSI-high and MSI stable. The results showed that MSI-high status was related to clinicopathologic parameters such as deep myometrial invasion and higher histologic grade in endometrioid type adenocarcinomas.

Intratumoral CD8+ Lymphocyte Infiltration as a Prognostic Factor and Its Relationship With Cyclooxygenase 2 Expression and Microsatellite Instability in Endometrial Cancer

2015 ◽  
Vol 25 (7) ◽  
pp. 1165-1172 ◽  
Author(s):  
Tomohiro Suemori ◽  
Nobuyuki Susumu ◽  
Takashi Iwata ◽  
Kouji Banno ◽  
Wataru Yamagami ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Microsatellite Instability ◽  
Antitumor Immunity ◽  
Proportional Hazards ◽  
Cyclooxygenase 2 ◽  
Repair System ◽  
Fisher Exact Probability Test ◽  
Exact Probability ◽  
Dna Mismatch Repair System ◽  
Cox 2

ObjectiveMicrosatellite instability (MSI) is caused by a defective DNA mismatch repair system. Colorectal cancer in MSI-positive patients is characterized by an increased number of tumor-infiltrating lymphocytes. On the other hand, it has recently been reported that cyclooxygenase 2 (COX-2) suppresses antitumor immunity. The objectives of the present study were to clarify the relationships among MSI status, COX-2 expression, and antitumor immune status and to verify impact of these factors on the prognosis of endometrial cancer.MethodsThe data of 123 patients with endometrial cancer were analyzed. The numbers of tumor-infiltrating CD8+T lymphocytes within cancer cell nests (TILs), as a representative of the antitumor immunity, and COX-2 expression levels in the tumor cells were analyzed by immunohistochemical staining. Microsatellite instability was evaluated by polymerase chain reaction analysis for 11 markers. Fisher exact probability test, Kaplan-Meier method, and proportional hazards analysis were used for the statistical analyses.ResultsThe MSI-positive tumors showed significantly higher grades (G2 or G3) and significantly larger numbers of TILs than did the MSI-negative tumors. The COX-2–high group showed significantly fewer TILs than did the COX-2–low group. Multivariate analysis identified a low number of TILs (<10), positive lymph node involvement, and high tumor malignancy grade as factors independently associated with poor prognosis. The prognosis was significantly poorer in the patients with MSI-positive tumors with high COX-2 expression than in those with MSI-positive tumors showing low COX-2 expression.ConclusionsThe number of TILs, which was increased by MSI and decreased by COX-2 expression, was associated with a poorer prognosis in patients with endometrial cancer. We also propose that COX-2 may block MSI-activated TILs in the tumor microenvironment.

Multipopulation Analysis of Polymorphisms in Five Mononucleotide Repeats Used to Determine the Microsatellite Instability Status of Human Tumors

2006 ◽  
Vol 24 (2) ◽  
pp. 241-251 ◽  
Author(s):  
Olivier Buhard ◽  
Francesca Cattaneo ◽  
Yick Fu Wong ◽  
So Fan Yim ◽  
Eitan Friedman ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Human Tumors ◽  
Human Populations ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System ◽  
Different Populations ◽  
Variant Alleles ◽  
Colorectal Cancer Patients

Purpose Human gastrointestinal tumors with inactivated DNA mismatch repair system (microsatellite instability [MSI] tumors) have distinct molecular and clinicopathologic profiles, and are associated with favorable prognosis. There is evidence suggesting that colorectal cancer patients with MSI tumors respond differently to adjuvant chemotherapy as compared with patients with non-MSI tumors. Finally, determination of the MSI status has clinical application for assisting in the diagnosis of suspected hereditary cases. It is thus becoming increasingly recognized that testing for MSI should be conducted systematically in all human cancers potentially of this type. We recently described a pentaplex polymerase chain reaction of five mononucleotide repeats to establish the MSI status of human tumors, and showed that this assay was 100% sensitive and specific. Moreover, these markers are quasimonomorphic in germline DNA of the white population (ie, individuals of Eurasian origin), and could be used for tumor MSI determination without the requirement for matching normal DNA in this group. Patients and Methods In this study, we analyzed a comparable panel of five mononucleotide markers in germline DNA from 1,206 individuals encompassing 55 different populations worldwide. Results With the exception of two Biaka Pygmies and one San individual for whom three markers showed variant alleles (three cases [0.2%]), the remaining 1,203 individuals showed no alleles of variant size (1,055 cases [87.5%]), or only one (122 cases [10.1%]) or two (26 cases [2.2%]) markers with variant alleles. All 60 MSI tumors investigated display instability in at least four of the five markers. Conclusion We demonstrated that tumor MSI status can be determined using the pentaplex reaction for all human populations without the need for matching normal DNA.

scholarly journals A tumor association to be aware: endometrial cancer and colon cancer in relation to lynch syndrome

2022 ◽  
Author(s):  
Behyamet Onka ◽  
Daoud ali Mohamed ◽  
Romeo Thierry Tessi Yehouenou ◽  
Boris Adeyemi ◽  
Wend-Yam Mohammed Traore ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Molecular Biology ◽  
Lynch Syndrome ◽  
Genetic Disorder ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System ◽  
Mutl Homolog 1 ◽  
Tumor Association

lynch syndrome (LS) is an autosomal dominant genetic disorder with incomplete penetration caused by a germline mutation in one of the genes of the deoxyribonucleic acid (DNA) mismatch repair system (MMR) namely: mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MHS6), post-meiotic segregation increased 1 homolog 2 (PMS2) or the EpCAM (Epithelial CellAdhesionMolecule) gene, which causes the inactivation of MSH2. Patients with this syndrome have a high relative risk of developing cancers at a young age, led by colorectal cancer (CRC) and endometrial cancer in females. The diagnosis is suspected when the patient’s personal and family history meets the Amsterdam or Bethesda criteria. It is guided by immunohistochemistry (IHC) and/or molecular biology that show loss of expression of one or more proteins of the MMR system and microsatellite instability on tumor DNA. In case of positive IHC and/or molecular biology, the patient should be referred to an oncogenetic consultation for a definitive diagnosis. We present the case of a 49-year-old patient who presented an anaemic syndrome in metrorrhagia. After a clinical, imaging, biological and anatomopathological examination, the diagnosis of LS was made.

Warthin Tumors Do Not Have Microsatellite Instability and Express Normal DNA Mismatch Repair Proteins

2006 ◽  
Vol 130 (1) ◽  
pp. 52-56 ◽  
Author(s):  
Jennifer L. Hunt
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Epithelial Component ◽  
Repair Enzymes ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System ◽  
Polymerase Chain

Abstract Context.—Warthin tumors are controversial entities with a poorly understood etiology. Although some investigators have suggested a neoplastic origin, others have supported a developmental anomaly. A recent study described the absence of staining for hMLH1 and hMSH2 proteins in the epithelial component of Warthin tumors, suggesting that they arise secondary to defects in the DNA mismatch repair system. Objective.—To determine if Warthin tumors exhibit evidence of DNA mismatch repair defects. Design.—Immunostains for hMLH1 and hMSH2 were performed using a standard approach. Microdissection of the epithelial component was followed by DNA extraction from the tissue fragments. Polymerase chain reaction and capillary electrophoresis analyses were performed for the following 5 National Cancer Institute–recommended microsatellites: D2s123, D5s346, D17s250, BAT25, and BAT26. Patients.—Twelve patients with Warthin tumors were included. Results.—The immunostains for hMLH1 and hMSH2 showed preserved expression in the nuclei of the epithelial component of all Warthin tumors. No microsatellite instability was detected, and no loss of heterozygosity was seen. Conclusions.—These results are not concordant with previously reported results showing loss of expression of the hMLH1 and hMSH2 DNA mismatch repair enzymes in the epithelial component of Warthin tumors. Furthermore, no microsatellite instability was detected in the 5 loci tested for each tumor in this series. These data demonstrate that Warthin tumors do not have evidence of DNA mismatch repair defects at the genomic or protein expression level.

Improved Survival With an Intact DNA Mismatch Repair System in Endometrial Cancer

2006 ◽  
Vol 108 (5) ◽  
pp. 1208-1215 ◽  
Author(s):  
David E. Cohn ◽  
Wendy L. Frankel ◽  
Kimberly E. Resnick ◽  
Vanna L. Zanagnolo ◽  
Larry J. Copeland ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

scholarly journals Immune Checkpoint Inhibition in Metastatic Colorectal Cancer Harboring Microsatellite Instability or Mismatch Repair Deficiency

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1149
Author(s):  
Romain Cohen ◽  
Raphaël Colle ◽  
Thomas Pudlarz ◽  
Maximilien Heran ◽  
Alex Duval ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Predictive Biomarker ◽  
Repair System ◽  
Comprehensive Overview ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Metastatic Setting ◽  
Future Challenges ◽  
Tumor Mutational Burden

Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10–18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs. In this review, we will present a comprehensive overview of the literature concerning the efficacy of ICIs in MSI/dMMR mCRC, with a focus on new developments in first-line metastatic setting. Then, we will present current and future challenges of immuno-oncology for patients with MSI/dMMR metastatic CRC.

Oxidative stress induces inactivation of the DNA mismatch repair system and causes microsatellite instability

2000 ◽  
Vol 118 (4) ◽  
pp. A707
Author(s):  
Christoph Gasche ◽  
Christina L. Chang ◽  
Jennifer Rhees ◽  
Ajay Goel ◽  
Luigi Ricciardiello ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

Functional Specifics of the MutL Protein of the DNA Mismatch Repair System in Different Organisms

2020 ◽  
Vol 46 (6) ◽  
pp. 875-890
Author(s):  
M. V. Monakhova ◽  
M. A. Milakina ◽  
R. M. Trikin ◽  
T. S. Oretskaya ◽  
E. A. Kubareva
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

scholarly journals Steady-state regulation of the human DNA mismatch repair system.

2000 ◽  
Vol 275 (37) ◽  
pp. 29178
Author(s):  
Dong Kyung Chang ◽  
Luigi Ricciardiello ◽  
Ajay Goel ◽  
Christina L. Chang ◽  
C. Richard Boland
Keyword(s):  
Steady State ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
State Regulation ◽  
Repair System ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

scholarly journals Evidence That the DNA Mismatch Repair System Removes 1-Nucleotide Okazaki Fragment Flaps

2015 ◽  
Vol 290 (40) ◽  
pp. 24051-24065 ◽  
Author(s):  
Lyudmila Y. Kadyrova ◽  
Basanta K. Dahal ◽  
Farid A. Kadyrov
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Okazaki Fragment ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System
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