All colorectal tumors arising before age 45 or tumors with positive family history.
Microsatellite analysis from tumor tissue
Clinical Features
The so-called microsatellite instability is typcially found in tumors arising within the HNPCC syndrome which is caused by defects in mismatch repair (MMR) genes. The functional loss of both alleles in a tumor cell causes defects in DNA repair following mitosis which is reflected by microsatellite instability. Microsatellites are repetitive DNA sequences in the genome which are particularly prone to defects during mitosis. In cells with defective DNA repair mechanisms the length of two corresponding microsatellites may therefore differ between tumor and normal tissues. More than 95% of tumors show microsatellite instability in the HNPCC syndrome. Tumors exhibiting microsatellite instability also exhibit pathohistological peculiarities such as a relatively common inflammatory infiltration with immunologically competent cells. Since the genetic abnormalities are also found in genes coding for surface proteins, the cells develop strong immunogenicity. The resulting inflammatory reactions may also explain the overall better 5 years survival time of these tumors.
Genetic Information
Genetic alterations underlying the HNPCC syndrome are found in the mismatch repair (MMR) genes including MLH1 (3p21.3), MSH2 (2p21-p22), MSH6 (2p16), and PMS2 (7p22).
Prevalence
In Germany, there are around 50.000 new cases of colorectal carcinoma per year. About 8% of cases are suggestive of a hereditary cancer. Among those 3-4% are caused by a genetic alteration in the mismatch repair genes.
Diagnostic
Indication
Method
Repetitive DNA sequences are amplified from DNA extracted both from the tumor tissue and from peripheral blood lymphocytes or from an alternative healthy tissue using PCR and compared using fragment length analysis.
Sample Requirement
Paraffin-embedded tumor tissue is microdissected and DNA is extracted from the tumor cells. For ordering the paraffin block we need the corresponding pathohistolgical diagnosis including the journal number and 2 to 4 ml of EDTA blood.
Duration
6 - 8 weeks