Microsatellite instability is used as an aid in the diagnosis of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) also know as Lynch syndrome. Microsatellites are also known as short tandem repeats found in human DNA as a regulatory and structural part of the human genome. These microsatellites are not longer than 2-6 base pairs in length found in 10-50 repeats. The regions of microsatellite instability are susceptible to mistakes during DNA replication that are typically repaired by mismatch repair proteins (MMR).
Mutation in MMR genes results in nonfunctional MMR proteins, which often results in accumulation of non-repaired, damaged mutated short tandem repeats leading to microsatellite instability (MSI). There are several MMR genes that are prone to mutations. The most common MMR are hMLH1, hMSH2, hPMS1, and hPMS2. Mutations on any of these genes or more than one gene can lead to MSI.
MSI is predominantly associated with polyposis and nonpolyposis colorectal cancer, especially with HNPCC. Hereditary nonpolyposis colorectal cancer (HNPCC) can be a component of Lynch syndrome. It is an autosomal dominant syndrome with early onset of colonic carcinoma and with increased risk for malignancy. Genetic testing for MMRs can confirm the diagnosis of HPNCC and can also identify presymptomatic individuals at risk among the patient's relatives. This test usually covers most common gene mutations (coding regions) in hMLH1, hMSH2, hPMS1, and hPMS2. Early screening can help in patients with family history of colorectal cancer.
Mutations of genes in hMLH1, hMSH2, hPMS1, and hPMS2 (one or more) are present in individuals with HNPCC
>30-40% : MSI-H phenotype
Negative for mutations analyzed
Real Time PCR, PCR with Allele Specific Primer Extension, Pyrosequencing, Chip array, Immunohistochemistry, FISH.
Carcinoembryonic Antigen (CEA), Chromosomal analysis, Occult blood, B-RAF mutation analysis, Microsatellite Instability/HNPCC by molecular method and by IHC, Septin 9 (SEPT9), K-RAS, EGFR Mutation Detection by molecular method, p53 by molecular method and by IHC, Ki67 by IHC, p63 by IHC.
|C18||Malignant neoplasm of colon|
|C18.0||Malignant neoplasm of cecum|
|C18.2||Malignant neoplasm of ascending colon|
|C18.4||Malignant neoplasm of transverse colon|
|C18.6||Malignant neoplasm of descending colon|
|C18.7||Malignant neoplasm of sigmoid colon|
|C18.8||Malignant neoplasm of overlapping sites of colon|
|C18.9||Malignant neoplasm of colon, unspecified|
|C19||Malignant neoplasm of rectosigmoid junction|
|C20||Malignant neoplasm of rectum|
|C54.1||Malignant neoplasm of endometrium|
|C54.9||Malignant neoplasm of corpus uteri, unspecified|
|C56||Malignant neoplasm of ovary|
|C57.00||Malignant neoplasm of unspecified fallopian tube|
|C57.01||Malignant neoplasm of right fallopian tube|
|C57.02||Malignant neoplasm of left fallopian tube|
|R97||Abnormal tumor markers|
|R97.0||Elevated carcinoembryonic antigen [CEA]|
|Z80.0||Family history of malignant neoplasm of digestive organs|
|Z85||Personal history of malignant neoplasm|
|Z85.0||Personal history of malignant neoplasm of digestive organs|
|Z85.42||Personal history of malignant neoplasm of other parts of uterus|
|Z85.44||Personal history of malignant neoplasm of other female genital organs|
|Z85.9||Personal history of malignant neoplasm, unspecified|