Cancers, Vol. 11, Pages 1567: Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer

Cancers, Vol. 11, Pages 1567: Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer Cancers doi: 10.3390/cancers11101567 Authors: Evrard Tachon Randrian Karayan-Tapon Tougeron Tumor DNA mismatch repair (MMR) deficiency testing is important to the identification of Lynch syndrome and decision making regarding adjuvant chemotherapy in stage II colorectal cancer (CRC) and has become an indispensable test in metastatic tumors due to the high efficacy of immune checkpoint inhibitor (ICI) in deficient MMR (dMMR) tumors. CRCs greatly benefit from this testing as approximately 15% of them are dMMR but only 3% to 5% are at a metastatic stage. MMR status can be determined by two different methods, microsatellite instability (MSI) testing on tumor DNA, and immunohistochemistry of the MMR proteins on tumor tissue. Recent studies have reported a rate of 3% to 10% of discordance between these two tests. Moreover, some reports suggest possible intra- and inter-tumoral heterogeneity of MMR and MSI status. These issues are important to know and to clarify in order to define therapeutic strategy in CRC. This review aims to detail the standard techniques used for the determination of MMR and MSI status, along with their advantages and limits. We review the discordances that may arise between these two tests, tumor heterogeneity of MMR and MSI status, and possible explanations. We also discuss the strategies designed to d...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research

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PB, Shia J, Schultz N, Garcia-Aguilar J, Diaz LA, Goodman K, Saltz LB, Weiser MR, Smith JJ, Stadler ZK Abstract PURPOSE: Evaluate response of mismatch repair deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: dMMR rectal tumors at Memorial Sloan Kettering were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty dMMR rectal cancer patients were identified by immunohistochemistry and/or microsatellite instability analysis, with initial treatment response compared to a matched pMMR rectal cancer cohort. Germline and somatic mutation analyses were evaluated....
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionWith the increase in daily use of next-generation sequencing (NGS) technology, it is thought that detection rate of both combined mutations and rare mutations will be increased.
Source: International Journal of Colorectal Disease - Category: Gastroenterology Source Type: research
Rationale: Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation-induced LS-associated endometrial cancer (LSAEC) was rarely reported. Patient concerns: A 26-year-old female patient suffered from prolonged menstrual period and increased menstrual flow for 2 months. Diagnoses: The patient was diagnosed with cervix CIN III, endometrial cancer (EC), anemia, and LS. Interventions: Total hysterectomy, bilateral salpingectomy, pelvic lymphadenectomy were performed for treatin...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
ConclusionTo optimize targeting and visualization of the surgical field in right pelvic sidewall/paracolic gutter, robotic arms can be placed in a straight line from above the pubic symphysis extending to the left subcostal line and between the midline vertical and midclavicular lines. Robotic tumor debulking should be considered in selected patients with recurrent ovarian cancer who present with oligo-metastatic disease, in the absence of carcinomatosis.
Source: Journal of Minimally Invasive Gynecology - Category: OBGYN Source Type: research
O, Duval A Abstract Microsatellite instability (MSI), which is caused by deficiency of the DNA mismatch repair (MMR) system, is the molecular abnormality observed in tumors associated with Lynch syndrome. Lynch syndrome represents one of the most frequent conditions of cancer predisposition in human, thus requiring specific care and genetic counseling. Moreover, research has recently focused increasingly on MMR deficiency due to its positive predictive value for the efficacy of immune checkpoints inhibitors (ICKi) in metastatic tumors, regardless of their primary origin. MSI has also been demonstrated to constitu...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
Abstract Microsatellites are short tandem repeat DNA sequences of one to tetra base pairs distributed throughout the human genome, both in coding and non-coding regions. Owing to their repeated structure, microsatellites are particularly prone to replication errors that are normally repaired by the Mismatch Repair (MMR) system. MMR is a very highly conserved cellular process, involving many proteins, resulting in the identification, and subsequent repair of mismatched bases, likely to have arisen during DNA replication, genetic recombination or chemical or physical damage. Proteins within the MMR system include ML...
Source: Acta Bio-Medica : Atenei Parmensis - Category: General Medicine Authors: Tags: Acta Biomed Source Type: research
ConclusionsdMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.
Source: Journal of Gastrointestinal Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: The finding of a dMMR CRC had consequences for decisions on chemotherapy in a relative high proportion of patients. We recommend testing in all patients with CRC independent of age at diagnosis, as proper treatment decisions and genetic counselling are very important. PMID: 29161904 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs.
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Original Research Source Type: research
ConclusionsMany experts and professional authorities have recommended a universal MSI testing in all individuals newly diagnosed with colorectal cancers.
Source: Journal of Gastrointestinal Cancer - Category: Cancer & Oncology Source Type: research
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