Biomarker: Microsatellite instability

Biomarker subtype: DNA

Clinical application: prognosis(unfavorable)

Histology type: endometrioid endometrial carcinoma

Country: South Korea

Region: Pocheon

Sample type : tissue

Clinical method: immunohistochemistry,DNA Extraction,PCR and MSI analysis(using National Cancer Institute-recommended 5 microsatellite markers)

Expression pattern : MSI-high

Expression elevation: Specimens showing MSI at 2 or more informative loci were classified as MSI-high, whereas specimens showing no MSI were classified as microsatellite stable. Specimens with instability at only one marker were classified as MSI-low. For statistical comparisons, microsatellite stable and MSI-low were grouped together as MSI( - ).

Description: the MSI may represent the poor prognostic impact on the endometrioid type endometrial adenocarcinoma.

Funtion description: Loss of PSMA expression in a subset of EAC cases could be due to epigenetic silencing.

Detailed Description: DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage.[PMID 20478261][PMID 17139333] Mismatch repair is strand-specific. During DNA synthesis the newly synthesised (daughter) strand will commonly include errors. In order to begin repair, the mismatch repair machinery distinguishes the newly synthesised strand from the template (parental). In gram-negative bacteria, transient hemimethylation distinguishes the strands (the parental is methylated and daughter is not). However, in other prokaryotes and eukaryotes, the exact mechanism is not clear. It is suspected that, in eukaryotes, newly synthesized lagging-strand DNA transiently contains nicks (before being sealed by DNA ligase) and provides a signal that directs mismatch proofreading systems to the appropriate strand. This implies that these nicks must be present in the leading strand, and evidence for this has recently been found.[PMID 17139333] Recent work[PMID 20713735] has shown that nicks are sites for RFC-dependent loading of the replication sliding clamp, proliferating cell nuclear antigen (PCNA), in an orientation-specific manner, such that one face of the donut-shape protein is juxtaposed toward the 3'-OH end at the nick. Loaded PCNA then directs the action of the MutLalpha endonuclease [PMID 16873062] to the daughter strand in the presence of a mismatch and MutSalpha or MutSbeta. Any mutational event that disrupts the superhelical structure of DNA carries with it the potential to compromise the genetic stability of a cell. The fact that the damage detection and repair systems are as complex as the replication machinery itself highlights the importance evolution has attached to DNA fidelity. Examples of mismatched bases include a G/T or A/C pairing (see DNA repair). Mismatches are commonly due to tautomerization of bases during DNA replication. The damage is repaired by recognition of the deformity caused by the mismatch, determining the template and non-template strand, and excising the wrongly incorporated base and replacing it with the correct nucleotide. The removal process involves more than just the mismatched nucleotide itself. A few or up to thousands of base pairs of the newly synthesized DNA strand can be removed.[wikipedia]