MLH1, MSH2, MSH6, PMS2
HNPCC (Hereditary non-polyposis colorectal cancer); Lynch syndrome; Mismatch repair gene mutations;
|I MSI||Microsatellite Instability Profile|
|I MLH1||Microsatellite Instability MLH1|
|I MSH2||Microsatellite instability MSH2, Melanocyte Stimulating Hormone, FE11|
|I MSH6||Microsatellite instability MSH6, BC/44|
|I PMS2||Microsatellite instability PMS2, A16-4|
Paraffin embedded tissue block
3 slides (3-5 uM) per marker on adhesion glass
Ship ambient. Protect from extreme temperature with an ice pack. Separate ice pack from specimen.
Inadequate fixation; Improper labeling
Marker and tissue specific
The importance of mismatch repair genes became apparent with the identification of the genetic basis for hereditary nonpolyposis colon cancer (HNPC). MSH-2 is involved in the initial cognition of mismatch nucleotides during the replication mismatch repair process. It is thought that after MSH-2 binds to a mismatched DNA duplex it is joined by a heterodimer of MLH-1 and PMSH, which together help facilitate the later steps in mismatch repair.
A subset of HNPCC patients as well as some colorectal cancer patients are predisposed to cancer caused by germline muatations in the DNA mismatch repair (MMR) genes. Identification of inherited MMR mutations, besides impacting care and survelillance of the patient also enables familial predictive testing.
Individuals with mutations in one of the MMR genes are defined as having Lynch Syndrome. The revised Bethesda guidelines established criteria to identify at risk individuals. It is generally recommended that patients at increased risk for Lynch syndrome undergo pre-screening with microsatellite instability analysis by immunohistochemistry. Loss of particular MMR protein can direct which genes to evaluate by germline mutation analysis.
Immunohistochemistry studies have further determined that the microsatellite instability phenotype in endometrial carcinoma is linked to defects in the MLH1/PMS2 gene.