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  • Microsatellite Instability, An Important Molecular Hallmark for Colorectal Cancer
  • Mahoora Rahimi,1 Fatemeh Keyfi,2,*
    1. Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
    2. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran


  • Introduction: The second deadliest and one of the most prevalent kinds of cancer is colorectal cancer (CRC), a diverse disease marked by a slow buildup of genetic and epigenetic alterations. Even though CRC is one of the most deadly types of cancer in the world, it is also one of the most treatable if caught early. Most colorectal cancers (CRCs) start as precursor lesions like adenoma and progress to adenocarcinoma. The identification of three distinct molecular carcinogenesis pathways: No.1 chromosomal instability No.2 microsatellite instability (MSI) No3. CpG island methylator phenotype account for about 85%, 15%, and 17% of cases, respectively. Most other malignancies as well as sporadic colon, stomach, and sporadic endometrial cancers have MSI. microsatellite instability is present in 15–25% of colorectal cancer cases. In CRC, determining the MSI status has therapeutic and prognostic significance. Additionally, tumor identification and categorization employ MSI detection as a diagnostic tool. Given the significance of this matter, we decided to compile and publish a summary of data about the diagnostic and therapeutic aspects of MSI to aid in the diagnosis of CRC.
  • Methods: In this research, from the 36 primary articles searched in online databases such as PubMed and Google Scholar during the last 5 years (2018-2023), according to the inclusion and exclusion criteria of the study (which was the English language and the time frame of the articles), the final 14 articles Related to the two main keywords colorectal cancer and microsatellite instability were selected and analyzed.
  • Results: Short repeating DNA sequences, known as microsatellites or Short Tandem Repeats (STRs), makeup approximately 3% of the human genome. Mutations in these sequences occur often. A genetic disorder called microsatellite instability (MSI) is brought on by a flaw in the DNA mismatch repair machinery. Errors that arise during DNA replication and recombination are often corrected by this system. The repair process is carried out by the proteins MutS and MutL in prokaryotes, and by their homologs, MSH2, MSH3, MSH6, MLH1, MLH2, and MLH3 in eukaryotes. MSI can be directly identified by PCR-based amplification of particular microsatellite sequences, which is the most widely used approach, or indirectly by immunohistochemistry (IHC) staining to examine the expression of mismatch repair proteins. The process of IHC analysis entails determining whether cells have mismatch repair proteins or not. The DNA mismatch repair system's functioning is assessed using antibodies against proteins such as MLH1, MSH2, PMS2, and MSH6. Most anomalies in the relevant genes and mutations in MLH1 and MSH2 can be found by employing IHC analysis with PMS2 and MSH6 antibodies. Screening for Lynch Syndrome is the primary goal of IHC and MSI. Globally, the practice of performing universal MSI/IHC testing on cancers is growing. Using fluorescent multiplex PCR-based techniques, the presence of distinct microsatellite markers with varying lengths in tumor cells is quantified in normal cells. Three dinucleotide repeats (D5S346, D2S123, and D17S250) and two mononucleotide repeats (BAT25 and BAT26) were initially suggested for the diagnosis of microsatellite instability in colorectal cancer. Three MSI phenotypes exist: Microsatellite Stable (MSS) if no instability is seen, MSI-high (MSI-H) if two or more markers are mutated, and MSI-low (MSI-L) if only one marker is mutated. The Bethesda panel was the name given to this panel. Nonetheless, subsequent research revealed that mononucleotide markers offer superior specificity and sensitivity, prompting the National Cancer Institute (NCI) to later modify the Bethesda criteria. Because these panels are more accurate at diagnosing MSI in CRCs, their use has expanded.
  • Conclusion: It is commonly known that there is a rising trend in the incidence and early death of CRC in individuals under 50. Due to the prognostic and predictive value of this tumor biomarker, patients with MSI are of particular interest among these molecular subgroups. This increasing trend has intensified the need for serious research focusing on identifying strategies for the prevention and early detection of this disease. When it comes to CRC, MSI is a noteworthy genetic marker that can help with diagnosis, prognosis, and chemotherapeutic therapy efficacy prediction. These days, certain tumor molecular features are the focus of drug development methods, and molecular approaches have been created for MSI detection.
  • Keywords: CRC, MSI, Genomic Instability, DNA MMR system