Stains & CD markers

Last author update: 1 June 2016
Last staff update: 18 June 2021

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PubMed search: MSH2 [title]

Sheren Younes, M.D., Ph.D.
Page views in 2022: 1,857
Page views in 2023 to date: 907
Cite this page: Younes S. MSH2. website. Accessed June 9th, 2023.
Definition / general
  • Protein is 104.7 kDa, 943 amino acids, located at chromosome 2p21
  • Formed of 16 exons, mRNA is 3145 base pairs
Essential features
  • One of the main genes of the MisMatch Repair family (MMR)
    • The four key genes identified to date are MutL Homologue 1 (MLH1), MutS Homologue 2 (MSH2), MutS Homologue 6 (MSH6) and PostMeiotic Segregation increased 2 (PMS2, homologous to the E. coli MMR genes)
    • Optimally functioning MMR is important for cancer avoidance and to maintain genomic stability by correcting single base mismatch and insertion deletion loops which results from DNA replication, genetic recombination or chemical or physical damage
    • The MSH2 and MSH6 proteins bind, forming a heterodimeric complex (mutSα) which identifies mismatched bases and initiates DNA repair
      • Mismatch binding results in an ATP dependent conformational change, with subsequent recruitment of mutLα, MLH1 and PMS2 heterodimers
      • Then DNA repair proteins are recruited to complete the process
    • MMR dysfunction causes microsatellite instability, which is characteristic feature of Lynch syndrome
      • Microsatellites are short tandem repeats (2-5 DNA bases) scattered mainly in noncoding DNA regions
      • Microsatellite instability (MSI) is defined as changes in length due to insertions or deletions of repeating units in a microsatellite; it is caused by defective MMR, and classified as MSI-H if more than 30-40% of investigated loci show MSI or MSI-L if less
Uses by pathologists
    MSH2 and disease
  • Lynch syndrome, hereditary non-polyposis colon cancer (HNPCC)
    • Autosomal dominant
    • Early age of onset
    • Familial predisposition
    • Colorectal carcinoma, gynecological and urological malignancies
    • Molecular definition is based on germline mutation in one of the 4 major genes forming MMR system, 40% is caused by MSH2
    • Diagnosis by
  • Muir-Torre syndrome
    • Autosomal dominant
    • Sebaceous neoplasms and visceral malignancies
    • Mainly caused by MSH2 mutation
  • MMR defect and sporadic colorectal cancer
    • 10 and 15% of sporadic colon cancers; this MSI phenotype is associated with proximal primary tumor location, high grade, mucinous pathology, early stage, females, smoking and older age at onset
    • Most are thought to arise from sessile serrated adenomas or polyps
    • The majority are caused by MLH1 methylation and inactivation
Clinical features
Case reports
  • Baicalein is a new molecule that is found to specifically shrinks MutSa-deficint xenografts tumor and inhibits growth of colon tumors in colon specific MSH2 knockout mice (Cancer Res 2016 Jun 4 [Epub ahead of print])
Microscopic (histologic) images

Images hosted on other servers:

Examples of MLH1,
MSH2, MSH6 and PMS2

Immunohistochemistry & special stains
  • Staining localization
    • Nuclear

  • MSH2 staining
    • IHC is a simple way to detect protein expression
    • Defective MMR will show loss of expression of the protein
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